反应详情

A solution of 102 (500 mg, 0.9 mmol) in dichloromethane (20 mL) was treated with BCl3 (9 ml, 9 mmol, 1 M in dichloromethane) at −60° C. under nitrogen for 30 min. The reaction was then quenched with methanol (20 mL). Volatiles were distilled out to give a residue, which was dissolved into methanol (5 mL) and neutralized with Con. NH4OH (2 ml, 26% aqueous solution). After concentration, the crude product was purified by a silica gel column, eluted with 10° A) methanol in dichloromethane to give a mixture of the two epimers; the two epimers were separated by Prep-HPLC with the following conditions: Agilent Prep 1200 Detecl): Column, SunFire Prep C18; mobile phase, Water with 0.05% ammonia and CH3CN; 5% CH3CN up to 60% in 8 min; Detector, 220 nm) to afford (3aR,5R,6S,7R,7aR)-5-((R)-1,2-dihydroxyethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a white solid (23.1 mg, 9%), Faster eluting isomer; (ES, m/z): [M+H]+ 279.0; 1H NMR (300 MHz, D2O) δ 6.17 (d, J=6.3 Hz, 1H), 4.13 (t, J=6.0 Hz, 1H), 3.95 (t, J=4.5 Hz, 1H), 3.78-3.83 (m, 1H), 3.61-3.71 (m, 2H), 3.50-3.54 (m, 2H), 2.88 (s, 6H); and (3aR,5R,6S,7R,7aR)-5-((S)-1,2-dihydroxyethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a white solid (37.5 mg, 13%), Slower eluting isomer; (ES, m/z): [M+H]+ 279.0; 1H NMR (300 MHz, D2O) δ 6.18 (d, J=6.3 Hz, 1H), 4.05 (t, J=6.0 Hz, 1H), 3.90 (t, J=5.1 Hz, 1H), 3.75-3.81 (m, 1H), 3.65-3.69 (m, 1H), 3.44-3.53 (m, 3H), 2.87 (s, 6H).

1. customThe reaction was then quenched with methanol (20 mL)
2. distillationVolatiles were distilled out
3. customto give a residue, which
4. concentrationAfter concentration
5. customthe crude product was purified by a silica gel column
6. washeluted with 10° A) methanol in dichloromethane
7. customto give
8. additiona mixture of the two epimers
9. customthe two epimers were separated by Prep-HPLC with the following conditions