反应详情

A half saturated solution of dry chlorine in carbon tetrachloride is added dropwise by syringe to a solution of (4-phenylbutyl)phosphinic acid, ethyl ether (0.95 g., 4.2 mmole) in 4 ml. of dry carbon tetrachloride under argon until the yellow color of excess chlorine persists. The mixture is evaporated to dryness (0.1 mm Hg.), the colorless residue is taken up in 6 ml. of dry tetrahydrofuran and treated with L-alanyl-L-proline, phenylmethyl ester, hydrochloride salt (1.0 g., 3.2 mmole). The resulting suspension is cooled to 0° (ice bath) under argon and treated dropwise with a solution of triethylamine (1.1 ml., 7.95 mmole) in 5 ml. of dry tetrahydrofuran over a 15 minute period. After the addition is complete, the mixture is allowed to come to room temperature and stirred for an additional 30 minutes. The mixture is diluted with ethyl acetate, filtered and evaporated to dryness. The residue is taken up in ethyl acetate, washed successively with 5% potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride, dried (Na2SO4) and evaporated. The residue is purified by flash chromatography on silica gel (95 g.) eluting first with acetone/hexane (2:3) then acetone/hexane (2:1) to give 1.35 g of 1-[N-[ethoxy(4-phenylbutyl)phosphinyl]-L-alanyl]-L-proline, phenylmethyl ester as a colorless viscous oil. Rf (dichloromethane/acetone, 2:1) is 0.24.

1. customThe mixture is evaporated to dryness (0.1 mm Hg.)
2. temperatureThe resulting suspension is cooled to 0° (ice bath) under argon
3. additionAfter the addition
4. customto come to room temperature
5. filtrationfiltered
6. customevaporated to dryness
7. washwashed successively with 5% potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride
8. dry with materialdried (Na2SO4)
9. customevaporated
10. customThe residue is purified by flash chromatography on silica gel (95 g.)
11. washeluting first with acetone/hexane (2:3)