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 1-{(S)-[methyl-((S)-1-phenyl-ethyl)-amino]-phenyl-methyl}-naphthalen-2-ol (prepared as described by Chan et al., J. Org. Chemistry 2003, 68, 1589-1590; 14.7 mg, 0.04 mmol) in toluene (0.5 mL) and DiMPEG (100 mg, 0.05 mmol) in toluene (0.5 mL) is 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 HCl (2 mL) and the mixture is extracted with EtOAc (5 mL), dried over anhydrous 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 94.3% ee and about 91.3% yield (the ee value is determined by HPLC using a Chiralcel OD-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 HCl (2 mL)
6. extractionthe mixture is extracted with EtOAc (5 mL)
7. dry with materialdried over anhydrous Na2SO4
8. customthe solvent is removed in vacuo
9. customThe purification of the residue by flash chromatography (EtOAc/hexane, 1:10)

ORD record

ord-14f22c73e8d145f18f779045dbedce70

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592487B2