Methyl 3-oxo-5-phenylpentanoate → 3-Hydroxy-5-phenyl-pentanoic acid methyl ester

To a stirred solution of (S)-(−)-α,α-diphenyl-2-pyrrolidinemethanol (770 mg, 3 mmol) in dry THF (100 mL) was added 2 M THF solution of borane-dimethylsulfide complex (11 mL, 22 mmol) at rt under N2. After being stirred at rt for 16 h, a solution of 3-Oxo-5-phenyl-pentanoic acid methyl ester (JACS, 1974, 1082-1087) (6.5 g, 31.5 mmol) in dry THF (20 mL) was added dropwise at rt over a period of 1 h. The resultant clear solution was stirred at rt for another 30 min and was then cooled to 0° C. in an ice bath. The reaction was quenched by the addition of MeOH (90 mL) and the reaction pot was concentrated under reduced pressure. The residue was taken up with EtOAc (200 mL) and washed successively with H2O (100 mL), citric acid (100 mL), 5% NaHCO3 (100 mL) and brine (100 mL). After being dried over Na2SO4, the solvent was removed to afford an oil. Flush column chromatography purification on silica gel gave 3-Hydroxy-5-phenyl-pentanoic acid methyl ester as an oil (3.3 g, 51%) with 92% e.e. (judged from the corresponding Mosher's ester). 1H NMR (300 MHz, CDCl3) δ1.6-1.9 (m, 2H), 2.4-2.6 (m, 2H), 2.65-2.9 (m, 2H), 3.05 (d, 1H, J=6), 3.7 (s, 3H), 3.95-4.10 (m, 1H), 7.10-7.35 (m, 5H). ESMS calcd (C12H16O3): 208.1; found: 209.1 (M+H)+.

1. stirringThe resultant clear solution was stirred at rt for another 30 min
2. temperaturewas then cooled to 0° C. in an ice bath
3. customThe reaction was quenched by the addition of MeOH (90 mL)
4. customthe reaction
5. concentrationpot was concentrated under reduced pressure
6. washwashed successively with H2O (100 mL), citric acid (100 mL), 5% NaHCO3 (100 mL) and brine (100 mL)
7. dry with materialAfter being dried over Na2SO4
8. customthe solvent was removed
9. customto afford an oil
10. customFlush
11. customcolumn chromatography purification on silica gel

ORD record

ord-e998879b48e34abc8864caba719e8bb8

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06677462B2