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

Under N2 atmosphere at 0° C., LDA (2 M solution in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 3.0 g, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) over 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl solution (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 solution (100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue (12.4 g) was purified twice by column chromatography (heptane:ethyl acetate=40:1) to give 205j (3.42 g, 45%) as a colorless liquid. 1H NMR (CDCl3): δ (ppm): 4.11 (q, J=7.2, 2 H), 3.40 (t, J=6.9, 2 H), 1.85 (quintet, J=6.9, 2 H), 1.52-1.47 (m, 2 H), 1.45-1.36 (m, 2 H), 1.35-1.20 (m, 6 H), 1.24 (t, J=7.2, 3 H), 1.15 (s, 6 H). 13C-NMR (CDCl3): δ (ppm): 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 solution (100 mL) and brine (100 mL)
5. dry with materialdried over anhydrous Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue (12.4 g) was purified twice by column chromatography (heptane:ethyl acetate=40:1)

ORD record

ord-214bfe36d21e4d26a69658a10097b487

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642653B2