反应详情

A solution of triethyl phosphonoacetate or methyl diethylphosphonoacetate (5.19 mmol) and (RS)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (1.843 g, 5.19 mmol) in DCM (5 mL) was added dropwise to a vigorously stirred mixture of 50% aq. NaOH (30 mL) and 50 mL DCM containing tetrabutylammonium iodide (1.0 g). After 3 hr, the layers were separated and the organic phase was washed with water (20 mL) and brine (10 mL) then dried (Na2SO4) and evaporated. The crude material was chromatographed (silica gel, 1:4 EtOAc/petroleum) to give either (RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid ethyl ester 77 or (RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid methyl ester RS-40 (˜85% yield in each case). Compound 77: 1H nmr (CDCl3) δ 1.28 (t, J=7.1 Hz, 3H), 1.40 (s, 9H), 2.84 (br d, J=6.2 Hz, 2H), 4.19 (q, J=7.1 Hz, 2H), 4.52 (br s, 2H), 5.05 (s, 2H), 5.86 (dd, J=1.5, 15.7 Hz, 1H), 6.91 (dd, J=4.8, 15.6 Hz, 1H), 6.92 (d, J=8.6 Hz, 2H), 7.09 (d J=8.7 Hz, 2H), 7.32-7.45 (m, 5H). 13C nmr (CDCl3) δ 66.1, 157.7, 154.9, 147.7, 137.0, 130.4, 128.6, 127.9, 127.4, 121.0, 115.1, 114.9, 79.8, 70.0, 60.4, 52.4, 40.0, 28.3, 14.2. Compound RS-40: 1H NMR (CDCl3) δ 1.40 (s, 9H), 2.80 (m, 2H), 3.70 (s, 3H), 4.52 (br s, 2H), 5.05 (s, 2H), 5.83 (d, J=15 Hz, 1H), 6.88 (d, J=8.7 Hz, 2H), 6.88 (d, J=15 Hz, 1H), 7.07 (d, J=8.7 Hz, 2H), 7.28-7.48 (m, 5H). 13C NMR (CDCl3) δ 28.5, 40.1, 51.8, 52.6, 70.2, 80.0, 115.1, 120.8, 127.6, 128.1, 128.7, 130.6, 137.1, 148.2, 155.1, 157.9, 166.8.

1. customthe layers were separated
2. washthe organic phase was washed with water (20 mL) and brine (10 mL)
3. dry with materialthen dried (Na2SO4)
4. customevaporated
5. customThe crude material was chromatographed (silica gel, 1:4 EtOAc/petroleum)