(S)-3-Chloro-1-phenylpropan-1-ol

Cat.NO.:A128157 Purity:95%

Product Details of [ 100306-34-1 ]

CAS No. :	100306-34-1
Formula :	C₉H₁₁ClO
M.W :	170.64
SMILES Code :	O[C@H](C1=CC=CC=C1)CCCl
MDL No. :	MFCD00013309
InChI Key :	JZFUHAGLMZWKTF-VIFPVBQESA-N
Pubchem ID :	2777894

Safety of [ 100306-34-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 100306-34-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.33
Num. rotatable bonds	3
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	46.98
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	20.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.05
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.02
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.02
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.49
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.67
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.25

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.38
Solubility	0.718 mg/ml ; 0.00421 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.07
Solubility	1.45 mg/ml ; 0.00847 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.29
Solubility	0.0875 mg/ml ; 0.000513 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.91 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12’782’590 molecules and tested on 40 external molecules (r² = 0.94)	1.59

Application In Synthesis of [ 100306-34-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 100306-34-1 ]
Downstream synthetic route of [ 100306-34-1 ]

[ 100306-34-1 ] Synthesis Path-Upstream 1~1

1
[ 100306-34-1 ]
[ 82248-59-7 ]

References:

[1] Journal of Organic Chemistry, 1988, vol. 53, # 13, p. 2916 – 2920.

[ 100306-34-1 ] Synthesis Path-Downstream 1~5

1
[ 30818-28-1 ]
[ 100306-34-1 ]
[ 1972-28-7 ]
[ 357404-43-4 ]

Yield	Reaction Conditions	Operation in experiment
72%	With triphenylphosphine; In tetrahydrofuran; toluene;	a 4-Chloro-2-[(1R)-3-chloro-1-phenylpropyl]oxy}benzonitrile (S)-alpha-(2-Chloroethyl)benzenemethanol (170 mg, 1.0 mmol), <strong>[30818-28-1]4-chloro-2-hydroxybenzonitrile</strong> (154 mg, 1.0 mmol.) and triphenylphosphine (260 mg, 1.0 mmol.) in dry tetrahydrofuran (5 ml) were stirred in an ice bath under nitrogen whilst diethyl azodicarboxylate (0.16 ml, 1.0 mmol.) was added. The reaction mixture was allowed to warn to room temperature and stirred for 3 days. The solvent was evaporated and the residue dissolved in toluene, added to the top of a flash chromatography column and eluted with 10percent ether/isohexane to give the product (220 mg, 72percent) as a viscous oil. 1H NMR 300 MHz (CDCl3) 7.21 (1H, d), 7.24-7.33 (5H, m), 6.92 (1H, d of d), 6.75 (1H, d), 5.43 (1H, m), 3.80 (1H, m), 3.56 (1H, m), 2.50 (1H, m), 2.18 (1H, m).

References: [1]Patent: US2003/158185,2003,A1 .

2
[ 936-59-4 ]
[ 613-87-6 ]
[ 100306-34-1 ]
[ 100306-33-0 ]
[ 93-55-0 ]

Yield	Reaction Conditions	Operation in experiment
	With yeast strain Aureobasidium pullulans CQA; at 28℃; for 48h;Microbiological reaction; Enzymatic reaction;	General procedure: Fresh plates of each yeast strain were streaked from the frozen stock in PDA. A single colony was used to inoculate 100mL of YM Broth. The culture was incubated at 28C and 150rpm for 48h and the cells were collected by centrifugation at 4000rpm and 4C for 15min. The pellet was washed three times with 50mL physiological serum. Afterward, 2g of yeast cells (wet weight) were suspended in 20mL of 10% dextrose solution and 30mg of the appropriate substrate were added. The culture was incubated at 28C and 150rpm in an orbital shaker ZHICHENG ZHWY-211B for 48h.
30%Chromat.; 23%Chromat.	With yeast culture of Candida viswanathii KCh 120; In acetone; at 25℃; for 6h;Microbiological reaction;	General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water,were inoculated with a suspension of microorganisms and then incubated for 3-7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHCl3(3*10 ml). The extracts were dried over MgSO4, concentrated in vacuo, and analyzed by GC. All the experiments were repeatedthree times.

References: [1]Journal of Molecular Catalysis B: Enzymatic,2014,vol. 102,p. 94 – 98.
[2]Tetrahedron Asymmetry,2014,vol. 25,p. 1264 – 1269.

3
[ 936-59-4 ]
[ 1565-74-8 ]
[ 613-87-6 ]
[ 100306-34-1 ]
[ 100306-33-0 ]
[ 93-55-0 ]

Yield	Reaction Conditions	Operation in experiment
21%Chromat.	With yeast culture of Aphanocladium album KCh 417; In acetone; at 25℃; for 144h;Microbiological reaction;	General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water,were inoculated with a suspension of microorganisms and then incubated for 3-7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHCl3(3*10 ml). The extracts were dried over MgSO4, concentrated in vacuo, and analyzed by GC. All the experiments were repeatedthree times.
33%Chromat.	With yeast culture of Saccharomyces cerevisiae KCh 464; In acetone; at 25℃; for 144h;Microbiological reaction;	General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water,were inoculated with a suspension of microorganisms and then incubated for 3-7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHCl3(3*10 ml). The extracts were dried over MgSO4, concentrated in vacuo, and analyzed by GC. All the experiments were repeatedthree times.
33%Chromat.	With yeast culture of Saccharomyces pastorianus KCh 906; In acetone; at 25℃; for 24h;Microbiological reaction;	General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water,were inoculated with a suspension of microorganisms and then incubated for 3-7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHCl3(3*10 ml). The extracts were dried over MgSO4, concentrated in vacuo, and analyzed by GC. All the experiments were repeatedthree times.

References: [1]Tetrahedron Asymmetry,2014,vol. 25,p. 1264 – 1269.
[2]Tetrahedron Asymmetry,2014,vol. 25,p. 1264 – 1269.
[3]Tetrahedron Asymmetry,2014,vol. 25,p. 1264 – 1269.

4
[ 936-59-4 ]
[ 1565-74-8 ]
[ 613-87-6 ]
[ 100306-34-1 ]
[ 93-55-0 ]

Yield	Reaction Conditions	Operation in experiment
7%Chromat.; 21%Chromat.	With yeast culture of Rhodotorula rubra KCh 4; In acetone; at 25℃; for 24h;Microbiological reaction;	General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water,were inoculated with a suspension of microorganisms and then incubated for 3-7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHCl3(3*10 ml). The extracts were dried over MgSO4, concentrated in vacuo, and analyzed by GC. All the experiments were repeatedthree times.

References: [1]Tetrahedron Asymmetry,2014,vol. 25,p. 1264 – 1269.

5
[ 40263-57-8 ]
[ 100306-34-1 ]
(R)-3-(3-chloro-1-phenylpropoxy)-2-iodopyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 – 20℃;	Step (a) (R)-3-(3-Chloro-l-phenylpropoxy)-2-iodopyridine: To a solution of (5)-3- chloro-l-phenylpropan-l-ol (5.11 g, 0.030 mol) in anhydrous THF (60 mL) is added PPh3 (8.0 g, 0.031 mol). The mixture is stirred at room temperature for 10 min, and then cooled to 0 C in an ice bath. 2-Iodopyridin-3-ol (7.0 g, 0.03 lmol) is added into the reaction mixture, followed by adding diisopropyl azodicarboxylate (9.4 mL, 0.047 mol) dropwise over 10 min. The mixture is stirred at room temperature overnight, and then diluted with ethyl acetate (300 mL), followed by washing successively with saturated NaHC03 aqueous solution and brine. The organic phase is evaporated to dryness and the obtained residue is purified by silica gel column chromatography to give ( ?)-3-(3-chloro-l-phenylpropoxy)-2-iodopyridine as an oil (9.11 g, 78% yield). MS (ESI) m/z 374.0 [M+H]+.

References: [1]Patent: WO2016/154027,2016,A1 .Location in patent: Paragraph 0060.

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