反应详情

温度

130 °C

In a 2 L RBF equipped with mechanical stir, condenser and N2 inlet, glycine (34 g, 0.45 mol) was added to B2 (280 g) followed by the addition of AcOH (500 mL). Reaction flask was heated in a 130° C. oil bath for 8 h. Solvent was removed on the rotary evaporator at 50-60° C. To the thick syrupy crude product was added heptane (1 L) and H2O (1 L) followed by the addition of NaHCO3 to adjust the pH to ˜8-9. The mixture gave a solid along with organic and aqueous layers. The organic and aqueous layers were decanted and the solid was slurried with 500 mL of 5% NaHCO3 solution. NaHCO3 layer was decant and sticky solid was suspended in 700 mL ethylacetate (EtOAc) and 300 mL of dichloromethane (DCM). The mixture was stirred for 20 min, filtered and the filter cake was washed with 1 L of DCM. The filtrate was concentrated and residue was pass through 330 g silica gel plug using 25/75 to 75/25 EtOAc/heptane (total of 8 L). Clean fractions were combined to give 58 g of pure product. An additional 13 g of −70% pure product was obtained from less pure fractions. Yield was 47% over two steps. 1H NMR (300 MHz, DMSO-d6) δ 3.45 (m, 1H), 3.6 (s, 3H), 3.8 (m, 1H), 4.8 (d, 1H), 5.3 (d, 1H), 6.8 (d, 2H), 7.1 (d, 2H), 7.7-7.5 (m, 3H), 8.9 (t, 1H).

1. customReaction flask
2. customSolvent was removed on the rotary evaporator at 50-60° C
3. additionTo the thick syrupy crude product was added heptane (1 L) and H2O (1 L)
4. additionfollowed by the addition of NaHCO3
5. customThe mixture gave a solid along with organic and aqueous layers
6. customThe organic and aqueous layers were decanted
7. customNaHCO3 layer was decant
8. filtrationfiltered
9. washthe filter cake was washed with 1 L of DCM
10. concentrationThe filtrate was concentrated