反应详情

To 13.70 g (32.60 mmol) of crude 10-(N-benzyloxycarbonylamino)-2-formylamino-3-hydroxy-4-methylene-decanoic acid ethyl ester in 137 ml of tetrahydrofuran there are added, under argon, 18.5 ml (156.4 mmol) of hexa-1,5-diene and then, dropwise at 10° within a period of 15 minutes, 6.1 ml (78.2 mmol) of thionyl bromide. The mixture is stirred for one hour at 10° and for 2 hours at room temperature and is then poured into 200 ml of ice-cold saturated sodium hydrogen carbonate solution; the organic phase is separated off and re-extracted once with dichloromethane. The organic phases are washed with ice-cold 0.5-normal sodium hydrogen carbonate solution and then with saturated sodium chloride solution, dried over sodium sulfate and concentrated to dryness by evaporation in vacuo at 40°. 64 ml (260 mmol) of triisopropyl phosphite (96%) are added immediately to the resulting crude 10-(N-benzyloxycarbonylamino)-4-bromomethyl-2-formylamino-dec-3-enoic acid ethyl ester (27 g, yellow honey), and the mixture is stirred for 17 hours at 80° under a pressure of approximately 100 mbar, the isopropyl bromide that forms being captured in a cold trap (CO2). The excess triisopropyl phosphite is then distilled off under reduced pressure and the evaporation residue (23 g) is purified by chromatography on a column filled with 650 mg of silica gel (0.04-0.063 mm) with ethyl acetate/methanol (95:5). 8.73 g of 10-(N-benzyloxycarbonylamino)-4-diisopropylphosphonomethyl-2-formylaminodec-3-enoic acid ethyl ester are obtained in the form of a yellowish honey.

1. customthe organic phase is separated off
2. extractionre-extracted once with dichloromethane
3. washThe organic phases are washed with ice-cold 0.5-normal sodium hydrogen carbonate solution
4. dry with materialwith saturated sodium chloride solution, dried over sodium sulfate
5. concentrationconcentrated to dryness by evaporation in vacuo at 40°
6. stirringthe mixture is stirred for 17 hours at 80° under a pressure of approximately 100 mbar
7. distillationThe excess triisopropyl phosphite is then distilled off under reduced pressure
8. customthe evaporation residue (23 g) is purified by chromatography on a column
9. additionfilled with 650 mg of silica gel (0.04-0.063 mm) with ethyl acetate/methanol (95:5)