反应详情

5-L three-neck flask was charged with a cold (<10° C.) solution of Compound 5 (about 0.59 mole, 168.95 g) in N,N-dimethylformamide (DMF) (about 2 L). Diphenylcarbamoyl chloride (0.73 mole, 168.92 g) then was added to the solution. The resulting mixture was maintained below 10° C., sodium hydride (NaH; 1.19 mole, 28.45 g) was added, in portions, over about 1.3 hours, and the reaction mixture was allowed to warm to ambient temperature overnight. Thin layer chromatography (TLC) indicated that some unreacted Compound 5 remained. The reaction mixture was recooled to about 10° C., and additional NaH (about 0.3 mole, 7.11 g) was added. The subsequent reaction was quenched with saturated aqueous ammonium chloride (NH4Cl; about 1.3 L) followed by the addition of 10% aqueous acetic acid (AcOH; 1 L), 20% AcOH (0.5 L), and EtOAc (4 L) to obtain a mixture having a pH of about 4 to 5. The solids present in the flask then were filtered, rinsed with EtOAc (500 mL) and DI water (500 mL), and dried by lyophilization to afford about 229 g of crude Compound 6 and a crude filtrate containing additional Compound 6. The crude Compound 6 was dissolved in dichloromethane (CH2Cl2; 3 L), back extracted with deionized (DI) water (500 mL) and brine (500 mL). The organic phase was dried over Na2SO4 (323.30 g) and filtered to afford a solution containing the bulk of the crude Compound 6.

1. temperatureThe resulting mixture was maintained below 10° C.
2. customwas recooled to about 10° C.
3. customThe subsequent reaction
4. customwas quenched with saturated aqueous ammonium chloride (NH4Cl; about 1.3 L)
5. additionfollowed by the addition of 10% aqueous acetic acid (AcOH; 1 L), 20% AcOH (0.5 L), and EtOAc (4 L)
6. customto obtain a mixture
7. filtrationThe solids present in the flask then were filtered
8. washrinsed with EtOAc (500 mL) and DI water (500 mL)
9. customdried by lyophilization