1,4-Dibromobutane → Tert-Butyl 1-(4-bromobutyl)cyclopropanecarboxylate

Under a N2 atmosphere at −60° C., a solution of tert-butyl cyclopropanecarboxylate (80.05 g, 0.507 mol) and 1,4-dibromobutane (219.3 g, 1.01 mol) in dry THF (800 mL) was added drop wise to a solution of LDA (2 M in THF/heptane/ethylbenzene, 380 mL, 0.76 mol) in 1.5 h. Stirring was continued for 5 h, during which the reaction mixture was allowed to slowly reach rt. After that, the reaction mixture was poured into saturated aqueous NH4Cl (1 L). The organic layer was separated and concentrated in vacuo to a smaller volume. The aqueous layer was extracted with Et2O (3×200 mL). The combined organic layers were washed with saturated aqueous NH4Cl (2×400 mL) and brine (400 mL), dried (Na2SO4) and evaporated in vacuo. The remaining residue was purified by fractional distillation under reduced pressure to give tert-Butyl 1-(4-bromo-butyl)-cyclopropanecarboxylate (51.4 g, 94% pure by GC, 34%) as a slightly yellow oil. bp: T=93-96° C. (p=0.075-0.087 Torr), 1HNMR (CDCl3): δ=3.40 (t, J=6.8 Hz, 2H), 1.85 (quintet, J=7.1 Hz, 2H), 1.65-1.46 (m, 4H), 1.43 (s, 9H), 1.12 (q, J=3.5 Hz, 2H), 0.60 (q, J=3.5 Hz, 2H). 13C NMR (CDCl3): δ=174.0, 79.8, 33.6, 33.2, 32.8, 27.9 (3×), 26.3, 23.9, 15.1 (2×). HRMS calcd for C12H2:BrO2 (MH+): 277.0803, found: 277.0807.

1. customwas allowed to slowly reach rt
2. customThe organic layer was separated
3. concentrationconcentrated in vacuo to a smaller volume
4. extractionThe aqueous layer was extracted with Et2O (3×200 mL)
5. washThe combined organic layers were washed with saturated aqueous NH4Cl (2×400 mL) and brine (400 mL)
6. dry with materialdried (Na2SO4)
7. customevaporated in vacuo
8. distillationThe remaining residue was purified by fractional distillation under reduced pressure

ORD record

ord-473df0c969a3416ead5fdce60c71c5a6

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08309604B2