Diisopropylamine → HCID 117698034, compound

Participants

Reaction Steps

To a solution of diisopropylamine (1.02 g, 10 mmol, 5.0 eq) in THF (10 mL) was added n-BuLi (5 mL, 2.0 M, 5.0 eq) dropwise at −50° C. After 30 min, dry EA (880 mg, 10 mmol, 5.0 eq) in NMP/THF (11 mL, 1:10) was added dropwise. After 1 h at −50° C., a solution of compound 116h (500 mg, 2 mmol, 1.0 eq) in THF (5 mL) was added slowly, and the resulting mixture was warmed from −50° C. to room temperature for 2 h. The reaction mixture was quenched with water (50 mL), extracted with EA (100 mL). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel (EA/PE=1:3) to give ethyl 2-(8-benzyl-6,6-difluoro-3-hydroxy-8-azabicyclo[3.2.1]octan-3-yl)acetate 116i as a colorless oil. 490 mg, yield: 72%. 1H NMR (400 MHz, DMSO-d6) ppm 7.37-7.19 (m, 5H), 4.45 (s, 1H), 4.09 (q, J=7.0 Hz, 2H), 3.84-3.70 (m, 2H), 3.27 (d, J=5.0 Hz, 1H), 3.08 (d, J=11.3 Hz, 1H), 2.70 (q, J=13.6 Hz, 1H), 2.43 (s, 2H), 2.37-2.26 (m, 1H), 2.13-2.00 (m, 2H), 1.84-1.72 (m, 1H), 1.52 (d, J=14.3 Hz, 1H), 1.22 (t, J=7.0 Hz, 3H); MS: calc'd (MH+) 340, measured (MH+) 340.

Provenance & Evidence