反应详情

A mixture of ethoxy(4-phenylbutyl)phosphinyl chloride [4.4 mmole; prepared as set forth in Example 1(f)], dry tetrahydrofuran (10 ml.), and 3-amino-2-oxo-hexahydro-1H-azepine-1-acetic acid, ethyl ester, monohydrochloride (1.0 g., 4.0 mmole) at 0° (ice bath) in an argon atmosphere is treated dropwise with triethylamine (1.7 ml., 3.0 eq.) in tetrahydrofuran (5 ml.) over 2 minutes. After 20 minutes, the ice bath is removed and the reaction mixture is stirred for an additional 1.5 hours. The reaction mixture is diluted with ethyl acetate and washed successively with saturated sodium bicarbonate, 5% potassium bisulfate, and brine, dried (MgSO4) and evaporated. The residue (2.1 g.) is chromatographed on silica (65 g.) eluting with ethyl acetate then acetone to give 1.0 g. of (S)-hexahydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-2-oxo-1H-azepine-1-acetic acid, ethyl ester as an oil after evaporation. TLC (ethyl acetate) single spot at Rf =0.1.

1. customprepared
2. customat 0°
3. customthe ice bath is removed
4. additionThe reaction mixture is diluted with ethyl acetate
5. washwashed successively with saturated sodium bicarbonate, 5% potassium bisulfate, and brine
6. dry with materialdried (MgSO4)
7. customevaporated
8. customThe residue (2.1 g.) is chromatographed on silica (65 g.)
9. washeluting with ethyl acetate
10. customacetone to give 1.0 g
11. customof (S)-hexahydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-2-oxo-1H-azepine-1-acetic acid, ethyl ester as an oil after evaporation