2-Chlorobenzaldehyde → 2-Chlorobenzhydrol, (2R)-

Temperature

60 °C

PhB(OH)2 (122 mg, 1.0 mmol) and ZnEt2 (334 μL, 3.25 mmol) in toluene (1 mL) is charged to a 10 mL flask under a nitrogin atmosphere. This mixture is heated to 60° C. and stirred for 10 h with a magnetic stirrer. Then the mixture is cooled to 0° C. and the title compound of Example 1, 1-{(S)-[methyl-((S)-1-phenyl-ethyl)-amino]-naphthalen-1-yl-methyl}-naphthalen-2-ol (16.7 mg, 0.04 mmol) in toluene (0.5 mL) and DiMPEG (100 mg, 0.05 mmol) in toluene (0.5 mL) are added. After stirring for additional 15 min, the solution is cooled to −15° C. and 2-chlorobenzaldehyde (70.0 mg, 0.5 mmol) in toluene (1 mL) is added. After stirring 15 h at −15° C., the reaction is quenched with 1 N hydrochloric acid (HCl, 2 mL) and the mixture is extracted with ethyl acetate (EtOAc, 5 mL), dried over anhydrous sodium sulfate (Na2SO4) and the solvent is removed in vacuo. The purification of the residue by flash chromatography (EtOAc/hexane, 1:10) gives (R)-(2-chlorophenyl)phenylmethanol in about 96.9% ee and about 91.1% yield (the ee value is determined by HPLC using a Chiralcel OB-H column).

1. temperatureThen the mixture is cooled to 0° C.
2. stirringAfter stirring for additional 15 min
3. temperaturethe solution is cooled to −15° C.
4. stirringAfter stirring 15 h at −15° C.
5. customthe reaction is quenched with 1 N hydrochloric acid (HCl, 2 mL)
6. extractionthe mixture is extracted with ethyl acetate (EtOAc, 5 mL)
7. dry with materialdried over anhydrous sodium sulfate (Na2SO4)
8. customthe solvent is removed in vacuo
9. customThe purification of the residue by flash chromatography (EtOAc/hexane, 1:10)

ORD record

ord-e1c5e7a740c24020b2c43b0768b82bcd

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592487B2