反応 #86669

反応方程式

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

溶媒

EtOAc

DMF

反応条件

後処理

1. 1
   その他This was partitioned between EtOAc and 1M hydrochloric acid
2. 2
   洗浄The organic phase was washed sequentially with 1M hydrochloric acid and brine
3. 3
   乾燥before being dried (MgSO4)
4. 4
   ろ過filtered
5. 5
   濃縮concentrated in vacuo
6. 6
   その他The crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether
7. 7
   その他to yield a white solid, 0.964 g, 76%

実験手順

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.

出典