Ethyl isobutyrate → Nonanoic acid, 9-bromo-2,2-dimethyl-, ethyl ester

Under a N2 atmosphere at 0° C., LDA (2 M in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) in 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) and dried. The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice to give 103g (3.42 g, 45%) as a colorless liquid. 1H NMR δ 4.11 (q, J=7.2 Hz, 2H), 3.40 (t, J=6.9 Hz, 2H), 1.85 (quintet, J=6.9 Hz, 2H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2 Hz, 3H), 1.15 (s, 6H). 13C NMR: δ 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034.

1. customthe temperature below 5° C
2. customThe layers were separated
3. extractionthe aqueous phase was extracted with Et2O (3×100 mL)
4. washThe combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL)
5. customdried
6. customThe remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice

ORD record

ord-4d59495eda7f418299fd9f06e0c2a9d2

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642653B2