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

Temperature

50 °C

PhB(OH)2 (122 mg, 1.0 mmol) and ZnMe2 (2.0 M solution in toluene, 1.6 mL)) is charged to a 10 mL flask under a nitrogin atmosphere. This mixture is heated to 50° C. and stirred for 8 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 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 97.0% ee and about 86.6% 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 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-7a3efbd06a9a4803847f59df3397b041

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592487B2