Methyl iodide → Ethyl 1-methylcyclobutane-1-carboxylate

Temperature

0 °C

A solution of ethyl cyclobutanecarboxylate (20.0 g, 156.0 mmol) in THF (160 mL) was added dropwise to a cold (−78° C.) solution of LDA (164 mmol of 2M solution) in THF (40 mL). The solution was warmed to 0° C. and then cooled again to −40° C. before the addition of iodomethane (10.2 mL, 163.8 mmol). The solution was slowly warmed to room temperature and stirred overnight. The reaction was quenched with an aqueous saturated solution of ammonium chloride and ether was added. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with 1N HCl then dried over MgSO4. The product was purified by distillation: 1H NMR (400 MHz, MeOD) δ 4.20-4.05 (m, 2H), 2.57-2.33 (m, 2H), 2.08-1.94 (m, 1H), 1.94-1.77 (m, 3H), 1.40 (s, 3H), 1.27 (tt, J=7.1, 1.5 Hz, 3H).

1. temperatureThe solution was slowly warmed to room temperature
2. customThe reaction was quenched with an aqueous saturated solution of ammonium chloride and ether
3. additionwas added
4. customThe layers were separated
5. washthe aqueous layer was washed with ether
6. washThe combined organic layers were washed with 1N HCl
7. dry with materialthen dried over MgSO4
8. distillationThe product was purified by distillation

ORD record

ord-270e6ffedb37477197d9bcaf44d25942

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394302B2