反应详情

To a solution of N-benzyl-serine benzyl ester (Intermediate 16, 6.35 g) in 90 ml of MeCN at ambient temperature was added 3-bromo-2-methyl-propene (5.6 ml), KI (740 mg) and K2CO3 (7.7 g). The reaction mixture was stirred at ambient temperature for 72 hrs. 1 ml of 3-bromo-2-methyl-propene was added and the reaction mixture was stirred for another 15 hrs. Only a small amount of starting material remained based on TLC (1:1; EtOAc-hexane). To the resulting mixture was added 11.2 g of iodine. After 4 hrs of stirring, TLC (10% EtOAc/hexane) showed complete conversion. The reaction mixture was partitioned into ether (300 ml) and 0.5 M Na2S2O3 (100 ml). The separated organic phase was washed successively with water, saturated NaHCO3 and brine, dried over MgSO4, and concentrated to dryness. The residue was purified on silica (5% EtOAc/Hexane) to give 6.65 g (yellowish oil, 64% yield, about 4:1 mixture) of compound 4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester. Major Component: 1H-NMR (300 MHz, CDCl3): δ 1.22 (s, 3H), 2.50 (d, 1H), 3.16-3.36 (m, 3H), 3.75-3.95 (m, 4H), 4.06 (dd, 1H), 5.16 (d, 1H), 5.21 (d, 1H), 7.28-7.36 (m, 10H).

1. stirringthe reaction mixture was stirred for another 15 hrs
2. stirringAfter 4 hrs of stirring
3. customThe reaction mixture was partitioned into ether (300 ml) and 0.5 M Na2S2O3 (100 ml)
4. washThe separated organic phase was washed successively with water, saturated NaHCO3 and brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated to dryness
7. customThe residue was purified on silica (5% EtOAc/Hexane)