Methyl iodide → HCID 23446871, compound

Temperature

0 °C

To a stirred solution of LDA (60 mL, 54 mmol, 1.0 M in THF (150 mL) at −78° C., was added ethyl 3-methylenecyclobutanecarboxylate (5.0 g, 35.7 mmol) and the reaction mixture was slowly allowed to warm to 0° C. and stir for 20 min. The reaction mixture was again cooled to −78° C. and MeI (8.92 mL, 143 mmol) was added and the reaction mixture was warmed to RT and stirred for 16 h. The reaction mixture was quenched with a saturated aq. solution of NH4Cl and the aqueous layer was extracted with diethyl ether (3×5 mL). The combined organic layer was washed with an aqueous solution of 1.5N HCl, brine, then dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 1% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 258A as a pale yellow liquid (3.5 g, 63%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.83-4.93 (m, 2H), 4.18 (q, J=7.18 Hz, 3.12-3.24 (m, 2H), 2.41-2.55 (m, 2H), 1.45 (s, 3H), 1.23-1.36 (m, 3H).

1. temperatureThe reaction mixture was again cooled to −78° C.
2. temperaturethe reaction mixture was warmed to RT
3. stirringstirred for 16 h
4. customThe reaction mixture was quenched with a saturated aq. solution of NH4Cl
5. extractionthe aqueous layer was extracted with diethyl ether (3×5 mL)
6. washThe combined organic layer was washed with an aqueous solution of 1.5N HCl, brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationthe filtrate concentrated
10. customThe crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 1% EtOAc in hexanes)
11. additionFractions containing the product
12. customevaporated

ORD record

ord-1e5cd33152b6420591eb48bf9285cff9

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2