반응 #1339115

반응 방정식

2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoic acid

L-methionine tert-butyl ester HCl

EDC

HOBT

HCl

→

tert-butyl (2S)-2- (2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1 -methylimidazol-5-yl)ethoxymethyl]benzoylamino}-4-methylsulfanylbutyrate

용매

ethyl acetate

DMF

반응 조건

후처리

1. 1
   기타The reaction was evaporated to dryness
2. 2
   세척washed with aqueous citric acid (1M, 10 ml)
3. 3
   추출extracted with dichloromethane (20 ml)
4. 4
   세척The extracts were washed with saturated brine
5. 5
   기타dried
6. 6
   여과filtered
7. 7
   기타Purification by flash column chromatography
8. 8
   세척eluting with dichloromethanel methanol (95:5, 9:1 and 85:15)
9. 9
   기타gave a gum
10. 10
    기타The resulting solid precipitate was isolated by centrifuging
11. 11
    세척further washing with diethyl ether
12. 12
    기타drying under high vacuum

실험 절차

A mixture of 2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoic acid (0.47 g, 1.06 mmol) (from Example 63), DMAP (0.62 g, 5.05 mmol), L-methionine tert-butyl ester HCl (0.62 g, 3.02 mmol), EDC (0.39 g, 2.02 mmol) and HOBT (0.137 g, 1.01 mmol) in DMF (25 ml) was stirred at ambient temperature under a nitrogen atmosphere for 16 hours. The reaction was evaporated to dryness and washed with aqueous citric acid (1M, 10 ml) and extracted with dichloromethane (20 ml). The extracts were washed with saturated brine, dried and filtered. Purification by flash column chromatography eluting with dichloromethanel methanol (95:5, 9:1 and 85:15) gave a gum. This was dissolved in ethyl acetate and treated with 1M ethereal HCl (10 ml). The resulting solid precipitate was isolated by centrifuging, further washing with diethyl ether and drying under high vacuum to give tert-butyl (2S)-2- (2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1 -methylimidazol-5-yl)ethoxymethyl]benzoylamino}-4-methylsulfanylbutyrate as a white solid, (0.366 g, 55%).

출처