Реакция #86669

Уравнение реакции

DIPEA

43

(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acid

amine

(S)-2-Amino-but-3-enoic acid methyl ester hydrochloride

HATU

→

(S)-2-((S)-2-{(S)-3-(4-Allyloxy-phenyl)-2-[(tert-butoxy-hydroxy-methyl)-amino]-propionylamino}-3-methyl-butyrylamino)-but-3-enoic acid methyl ester

Растворители

EtOAc

DMF

Условия реакции

Обработка

1. 1
   ДругоеThis was partitioned between EtOAc and 1M hydrochloric acid
2. 2
   ПромывкаThe organic phase was washed sequentially with 1M hydrochloric acid and brine
3. 3
   Сушкаbefore being dried (MgSO4)
4. 4
   Фильтрацияfiltered
5. 5
   Концентрированиеconcentrated in vacuo
6. 6
   ДругоеThe crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether
7. 7
   Другоеto yield a white solid, 0.964 g, 76%

Методика

Acid 43 (1.03 g, 2.45 mmol), amine 63 (1.1 equiv) and HATU (1.1 equiv) were dissolved in anhydrous DMF (0.10-0.50M relative to acid). DIPEA was added (4 equiv) and the reaction mixture stirred at rt for 18 h. This was partitioned between EtOAc and 1M hydrochloric acid. The organic phase was washed sequentially with 1M hydrochloric acid and brine before being dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether to yield a white solid, 0.964 g, 76%. Rf=0.46 (1/1 EtOAc/(50/70) petroleum ether). m.p. 104-106° C.

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