反应详情

温度

60 °C

DMF (anhydrous, 70 mL) was added to carbamate residue 3a (7.5 g, 19.7 mmol) and the mixture was cooled to 0° C. t-BOC-(1R)-amino-2-amino-1-phenylethane acetate salt (6.41 g, 21.6 mmol) was added followed by K2CO3 (4.08 g, 29.6 mmol). The mixture was stirred for ˜3 hours (all carbamate 3a (tR=11.5 minute in HPLC method 1) was converted to urea intermediate (tR=10.5 minute in HPLC method 1)). The temperature was raised to 60° C. to control the CO2 release. The mixture was heated for 2-3 hours then 210 mL of water was slowly added over 30-60 minutes maintaining the temperature at 60° C. The slurry was stirred for 30-60 minutes at 50-60° C. and was cooled down to 25° C. over 30-60 minutes. The slurry was filtered and the cake was washed with 210 mL water to remove the residual base. The cake was dried at 10 mm/50° C. to give 6.5 g (70% yield) of off-white fine needle crystal 3b. Alternately, the cake may be washed with acetonitrile/water 2:1 before drying.

1. additionwas added
2. temperatureThe mixture was heated for 2-3 hours
3. temperaturemaintaining the temperature at 60° C
4. temperaturewas cooled down to 25° C. over 30-60 minutes
5. filtrationThe slurry was filtered
6. washthe cake was washed with 210 mL water
7. customto remove the residual base
8. customThe cake was dried at 10 mm/50° C.