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 solution was cooled to approximately 0° C. and a solution of 1-(2-bromo-5-chlorophenyl)ethanone (3-3) (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 3-4 as a colorless solid (25.8 g; 98:2 S/R enantiomeric 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-f1b6cf3d672c4854a0784922978c6683

Quelldatensatz

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06818658B2