alpha-(4-chlorophenyl)pyridine-2-methanol Chemical Properties

Melting point:

78-80?C

Boiling point:

364.3±32.0 °C(Predicted)

Density 

1.275±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

12.46±0.20(Predicted)

color 

Off-White to Grey

InChI

InChI=1S/C12H10ClNO/c13-10-6-4-9(5-7-10)12(15)11-3-1-2-8-14-11/h1-8,12,15H

InChIKey

ZFUPOFQRQNJDNS-UHFFFAOYSA-N

SMILES

C(C1N=CC=CC=1)(C1C=CC(Cl)=CC=1)O

Safety Information

HS Code 

2933399090

alpha-(4-chlorophenyl)pyridine-2-methanol Usage And Synthesis

Chemical Properties

Light-Brown Solid

Uses

α-(4-Chlorophenyl)-2-pyridinemethanol is used as a reagent in the synthesis of Carbinoxamine (Maleate salt: C175920), a histamine H1 antagonist. α-(4-Chlorophenyl)-2-pyridinemethanol is also an intermediate in the synthesis of Bepotastine besylate (B317000), a non-sedating H1-antagonist that has anti-inflammatory activity.

Synthesis

Magnesium chips (5.37 g, 223.75 mmol, 3.0 eq.) were suspended in anhydrous tetrahydrofuran (60 mL) under argon protection and the reaction was initiated by the addition of iodine crystals (2) and 1,2-dibromoethane (2 drops). Subsequently, anhydrous tetrahydrofuran solution of 4-bromochlorobenzene (25.76 g, 134.39 mmol, 1.8 eq.) was slowly added dropwise for 1 h at room temperature. After the dropwise addition, the reaction mixture was continued to be stirred at room temperature for 1 hour. Next, anhydrous tetrahydrofuran (19 mL) solution of pyridine-2-carboxaldehyde (8 g, 74.68 mmol) was added dropwise at the same temperature, and stirring was continued for 2 hours after completion of the dropwise addition. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel column chromatography with 40% ethyl acetate/hexane as eluent afforded 12.26 g of (4-chlorophenyl)(pyridin-2-yl)methanol in 75% yield.ESI-MS: m/z 220 ([M+H]+).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 12, p. 3044 - 3047
[2] Journal of Medicinal Chemistry, 2007, vol. 50, # 2, p. 219 - 232
[3] Patent: WO2016/100823, 2016, A1. Location in patent: Page/Page column 115; 116
[4] Patent: US2006/100243, 2006, A1. Location in patent: Page/Page column 7; sheet 1

alpha-(4-chlorophenyl)pyridine-2-methanol(27652-89-7)Related Product Information

• p-Menthene-8-thiol
• 2-(4-BIPHENYLYL)-2-PROPANOL
• carbinoxamine
• BEPOTASTINE BESILATE
• BEPOTASTINE
• CARBINOXAMINE MALEATE SALT
• 8-Chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol
• alpha-(4-chlorophenyl)pyridine-2-methanol
• Rotoxamine
• 4-CHLORO-2-METHYLPHENYL-(2-PYRIDYL)METHANOL
• Pyridinemethanol, alpha-(p-chlorophenyl)-alpha-(dimethylaminoethyl)-, hydrochloride
• 8-Chloro-3-methoxy-11-(1-methyl-4-piperidinyl)-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-ol
• dazadrol
• [3-(2,4-DICHLOROPHENOXY)-5-(TRIFLUOROMETHYL)-2-PYRIDINYL](2,4-DICHLOROPHENYL)METHANOL
• 4-CHLORO-3-FLUOROPHENYL-(2-PYRIDYL)METHANOL
• 4-CHLORO-3-METHYLPHENYL-(2-PYRIDYL)METHANOL
• (4-CHLOROPHENYL)(1-ISOQUINOLINYL)METHANOL
• [3-CHLORO-5-(TRIFLUOROMETHYL)-2-PYRIDINYL](2,4-DICHLOROPHENYL)METHYL N-[3-(TRIFLUOROMETHYL)PHENYL]CARBAMATE