tert-Butyl acetate → 5-Hydroxy-3-oxo-7-phenyl-heptanoic acid tert-butyl ester

Temperature

-78 °C

A solution of 2.0 M LDA in heptane/THF/ethylbezene (9.4 mL, 18.8 mmol) was added slowly to a stirred solution of tert-butylacetate (2.18 g, 18.8 mmol) in dry THF (20 mL) under N2 at −78° C. After being stirred at −78° C. for 25 min., a solution of the above made 3-hydroxy-5-phenyl-pentanoic acid methyl ester (1.3 g, 6.25 mmol) in dry THF (10 mL) was then added through a cannula. The resultant clear solution was stirred at −78° C. for 1 h and then at −55° C. for another 1 h. The reaction was quenched by the addition of 20% aqueous acetic acid (20 mL). Two layers were separated and the aqueous layer was extracted with EtOAc (3×30 mL). Combined organic layer was washed with H2O (50 mL, brine (50 mL, dried with sodium sulfate, and then concentrated to leave an oil. Flush column chromatography purification on silica gel (4:1 Hexane/EtOAc to 2:1 Hexane/EtOAc) afforded the intermediate 5-Hydroxy-3-oxo-7-phenyl-heptanoic acid tert-butyl ester as a colorless oil (1.74 g, 95%). 1H NMR (300 MHz, CDCl3) δ1.45 (s, 9H), 1.6-1.9 (m, 2H), 2.50-2.85 (m, 4H), 3.35 (s, 3 H), 3.95-4.10 (m, 1H), 7.10-7.30 (m, 5H). ESMS calcd (C17H24O4): 292.2; found: 291.2 (M−H)+.

1. additionwas then added through a cannula
2. stirringThe resultant clear solution was stirred at −78° C. for 1 h
3. waitat −55° C. for another 1 h
4. customThe reaction was quenched by the addition of 20% aqueous acetic acid (20 mL)
5. customTwo layers were separated
6. extractionthe aqueous layer was extracted with EtOAc (3×30 mL)
7. washCombined organic layer was washed with H2O (50 mL, brine (50 mL
8. dry with materialdried with sodium sulfate
9. concentrationconcentrated
10. customto leave an oil
11. customFlush
12. customcolumn chromatography purification on silica gel (4:1 Hexane/EtOAc to 2:1 Hexane/EtOAc)

ORD record

ord-8bdc3020271748779a4ebd062071dbc6

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06677462B2