反应详情

A mixture of crude chloro (4-phenylbutyl)phosphinic acid, ethyl ester (2.44 mmole), dry tetrahydrofuran (10 ml.), and (±)-3-amino-3,4-dihydro-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester (0.65 g., 2.05 mmole) at 0° (ice bath) in an argon atmosphere is treated dropwise with triethylamine (0.86 ml., 3.0 eq.) in tetrahydrofuran (5 ml.) over 1 minute. After standing at 0° for 20 minutes the ice bath is removed and the reaction mixture is stirred for 16 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 (1.2 g.) is chromatographed on silica (60 g.) eluting with acetone/hexane (1:1) to give 0.8 g. of (±)-dihydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester as an oil after evaporation. TLC (acetone/hexane; 2:1) two spots at Rf =0.59,0.65(isomers at phosphorus).

1. customthe ice bath is removed
2. additionThe reaction mixture is diluted with ethyl acetate
3. washwashed successively with saturated sodium bicarbonate, 5% potassium bisulfate and brine
4. dry with materialdried (MgSO4)
5. customevaporated
6. customThe residue (1.2 g.) is chromatographed on silica (60 g.)
7. washeluting with acetone/hexane (1:1)
8. customto give 0.8 g
9. customof (±)-dihydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester as an oil after evaporation