Trimethyl borate → (alphaR)-2-Bromo-5-chloro-alpha-methylbenzenemethanol

Temperatur

0 °C

Trimethylborate (1.74 mL, 15.4 mmol) was added to a stirred solution of (S)-(−)-alpha,alpha-diphenyl-2-pyrrolidinemethanol (3.24 g, 12.8 mol) in tetrahydrofuran (350 mL) at room temperature. After 1.25 h, borane-methyl sulfide complex (70.4 mL of a 2M solution in tetrahydrofuran, 0.141 mol) was added slowly and a gentle effervesence was observed. The resulting soution was cooled to approximately 0° C. and a solution of 1-(2-bromo-5-chlorophenyl)ethanone (˜30.0 g, 0.128 mmol) in tetrahydrofuran (150 mL) was then added uniformly over 1 h. After the addition, the resulting mixture was allowed to warm to ambient temperature and aged overnight. The reaction mixture was concentrated under reduced pressure to approximately one quarter of its original volume, poured into 1N hydrochloric acid and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (9% ethyl acetate/hexanes as eluent) afforded the title compound as a colorless solid (98:2 enantiomer ratio).

1. additionAfter the addition
2. temperatureto warm to ambient temperature and aged overnight
3. concentrationThe reaction mixture was concentrated under reduced pressure to approximately one quarter of its original volume
4. additionpoured into 1N hydrochloric acid
5. extractionextracted three times with ethyl acetate
6. washThe combined organic extracts were washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customPurification of the crude residue by flash chromatography on silica gel (9% ethyl acetate/hexanes as eluent)

ORD-Eintrag

ord-09fe308150524b30a90a14bee2909575

Quelldatensatz

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07012084B2