تفاعل #61118

معادلة التفاعل

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

المردود 58.0%

المذيبات

trifluoroacetic acid

dichloromethane

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىpartitioned 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
   أخرىthe organic layer collected
4. 4
   تجفيفdried over sodium sulfate
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated
7. 7
   أخرىThe residue was without further purification
8. 8
   workup.DISSOLUTIONdissolved in tetrahydrofuran (50 mL)
9. 9
   درجة الحرارةthe resulting solution cooled to 0° C
10. 10
    workup.STIRRINGafter stirring overnight the reaction mixture
11. 11
    أخرىwas evaporated
12. 12
    أخرىthe residue was purified by chromatography over silica gel gradient
13. 13
    غسيلeluted with 0 to 100% ethyl acetate in hexanes

الإجراء التجريبي

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%).

المصدر