Methyl chloroformate → Methyl 2-cyanoadamantane-2-carboxylate

To a solution of adamantane-2-carbonitrile (1.17 g, 7.23 mmol) in anhydrous tetrahydrofuran (75 mL) was added lithium diisopropylamide (2.0 M solution in tetrahydrofuran, ethylbenzene and heptanes, 5.4 mL, 11.00 mmol)-78° C. The reaction mixture was stirred under a nitrogen atmosphere for 30 minutes, and then methyl chloroformate (0.83 mL, 11.00 mmol) was added. After 1.5 hour, the reaction was warmed to ambient temperature and quenched by addition of 1 M hydrochloric acid (150 mL). The mixture was diluted with ethyl acetate (200 mL), washed with 1 M hydrochloric acid (150 mL), brine (150 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes to afford the title compound as a colorless oil (0.95 g, 60%): 1H NMR (300 MHz, CDCl3) δ 3.80 (s, 3H), 2.51 (br s, 2H), 2.23-2.18 (m, 2H), 1.93-1.91 (m, 1H), 1.85-1.71 (m, 9H); MS (ES−) m/z 220.2 (M+1).

1. waitAfter 1.5 hour
2. customquenched by addition of 1 M hydrochloric acid (150 mL)
3. additionThe mixture was diluted with ethyl acetate (200 mL)
4. washwashed with 1 M hydrochloric acid (150 mL), brine (150 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo to dryness
8. customThe residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes

ORD record

ord-b5aec0d0da904d3685cd3a47d126edc8

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2