反应详情

To a solution of [(3R,4S,5S)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester (1 g, 2.47 mmol) and (R)-1,1,1-trifluoro-3-methoxy-propan-2-ol (392 mg, 2.72 mmol) in THF (13 mL) was added tert-BuOK (277 mg, 2.47 mmol) in small portions at 0° C. over a period of 30 min. After 1 h the cooling bath was removed and the orange solution was stirred at room temperature for 5 h. The reaction mixture was diluted with EtOAc (500 mL) and washed with ice cooled K2CO3 solution and cold brine. The organic phase was dried over Na2SO4, filtered and evaporated to yield a brown-yellowish foam: TLC Rf=0.50 (toluene-ETA 85:15); HPLC RtE=1.157 min; ESIMS [M+H-Boc]+=429; 1H NMR (600 MHz, DMSO-d6): δ 7.28 (s, 1H), 7.10 (d, 1H), 6.71 (d, 1H), 5.65 (broad, 1H), 4.95 (d, 1H), 3.83 (dd, 1H), 3.73 (dd, 1H), 3.42 (m, 1H), 3.31 (s, 3H), 3.25 (dd, 1H), 2.93 (m, 1H), 2.54 (d, 1H), 2.48-2.35 (m, 2H), 2.32-2.20 (m, 2H), 1.94 (m, 1H), 1.37 (s, 9H).

1. customAfter 1 h the cooling bath was removed
2. additionThe reaction mixture was diluted with EtOAc (500 mL)
3. washwashed with ice
4. temperaturecooled K2CO3 solution and cold brine
5. dry with materialThe organic phase was dried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customto yield a brown-yellowish foam
9. customHPLC RtE=1.157 min