反応 #61118

反応方程式

2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

di-tert-butyldicarbonate

→

2-{(2S,3S)-2-[(R)-2-(4-amino-phenyl)-2-tert-butoxycarbonylamino-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

収率 58.0%

溶媒

trifluoroacetic acid

dichloromethane

tetrahydrofuran

反応条件

後処理

1. 1
   その他partitioned between ethyl acetate and saturated aqueous sodium carbonate
2. 2
   workup.ADDITIONThe aqueous layer was adjusted to pH=9 by the addition of solid sodium carbonate
3. 3
   その他the organic layer collected
4. 4
   乾燥dried over sodium sulfate
5. 5
   ろ過filtered
6. 6
   濃縮concentrated
7. 7
   その他The residue was without further purification
8. 8
   workup.DISSOLUTIONdissolved in tetrahydrofuran (50 mL)
9. 9
   温度the resulting solution cooled to 0° C
10. 10
    workup.STIRRINGafter stirring overnight the reaction mixture
11. 11
    その他was evaporated
12. 12
    その他the residue was purified by chromatography over silica gel gradient
13. 13
    洗浄eluted with 0 to 100% ethyl acetate in hexanes

実験手順

2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (510 mg, 0.76 mmol) was dissolved in 30% v/v trifluoroacetic acid in dichloromethane solution (10 mL) at 0° C. The mixture was stirred at 0° C. for 2.5 hours and then partitioned between ethyl acetate and saturated aqueous sodium carbonate. The aqueous layer was adjusted to pH=9 by the addition of solid sodium carbonate and the organic layer collected, dried over sodium sulfate, filtered and concentrated. The residue was without further purification dissolved in tetrahydrofuran (50 mL) and the resulting solution cooled to 0° C. A solution of di-tert-butyldicarbonate (167 mg, 0.76 mmol) in tetrahydrofuran (5 mL) was added dropwise and after stirring overnight the reaction mixture was evaporated and the residue was purified by chromatography over silica gel gradient eluted with 0 to 100% ethyl acetate in hexanes to afford 2-{(2S,3S)-2-[(R)-2-(4-amino-phenyl)-2-tert-butoxycarbonylamino-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester as a white solid (250 mg, 58%).

出典