反应详情

A solution of N-[5-(bromoacetyl)-2-hydroxyphenyl]methanesulfonamide (J. Med. Chem. 1967, 10, 462-72) (1.15 g) in dry DMF (30 mL) was treated with diisopropylethylamine (1.06 mL) and (S)-phenylglycinol (474 mg) and the reaction mixture stirred at room temperature for 4 h. The reaction mixture was concentrated in vacuo and the residue re-suspended in methanol (50 mL). The reaction mixture was cooled to 0° C. and treated with CaCl2 (1.27 g). The reaction mixture was stirred at 0° C. for 30 min prior to portionwise addition of NaBH4 (218 mg) ensuring that the temperature did not rise above 10° C. After complete addition the reaction mixture was allowed to warm to room temperature and stirred for a further 74 h. The reaction mixture was concentrated in vacuo and the residue partitioned between EtOAc and water. The organic phase was dried and concentrated in vacuo. The mixture was purified by chromatography (SPE, gradient from DCM to DCM-MeOH—NH3(aq) 100:10:1) afforded the title compound (85 mg). LCMS RT=2.48 min

1. concentrationThe reaction mixture was concentrated in vacuo
2. temperatureThe reaction mixture was cooled to 0° C.
3. additiontreated with CaCl2 (1.27 g)
4. stirringThe reaction mixture was stirred at 0° C. for 30 min
5. additionto portionwise addition of NaBH4 (218 mg)
6. customdid not rise above 10° C
7. additionAfter complete addition the reaction mixture
8. temperatureto warm to room temperature
9. stirringstirred for a further 74 h
10. concentrationThe reaction mixture was concentrated in vacuo
11. customthe residue partitioned between EtOAc and water
12. customThe organic phase was dried
13. concentrationconcentrated in vacuo
14. customThe mixture was purified by chromatography (SPE, gradient from DCM to DCM-MeOH—NH3(aq) 100:10:1)