反应详情

温度

-8 °C

To a solution of cholic acid methyl ester (1000.0 g, 2.366 mol) in pyridine (2250 mL) at −10° C. was added a solution of p-toluenesulfonyl chloride (654.2 g, 2.431 mol) in pyridine (650 mL) dropwise over 2.5 hours while maintaining the reaction temperature at −10 to −6° C. The solution was mixed at −10° C. for an additional 12.5 hours, diluted with water (61.8 g) with continued cooling. The mixture at −7.5° C. was added over a period of 43 minutes to a mixture of MTBE (5 L) and 6N HCl (6.2 L). The layers were separated and the organic phase was washed with 7% NaHCO3 (2 L), followed by 2% NaCl (2 L), and finally with pH 7 phosphate buffer (2 L). The organic phase was filtered, concentrated under reduced pressure with MTBE (3×200 mL) to give 1608.93 g of a very viscous pale-straw colored oil (95.3% potency adjusted yield) that was used directly in the next step. 1H NMR (CDCl3, 400 MHz) δ 7.79 (d, J=8.5 Hz, 2H), 7.32 (d, J=8.6 Hz, 2H), 4.40-4.31 (m, 1H), 3.97 (br s, 9H), 3.83 (br s, 1H), 3.68 (s, 3H), 2.60-2.50 (m, 1H), 2.45 (s, 3H), 2.43-1.34 (m, 25H), 0.99 (d, J=6.3 Hz, 3H), 0.88 (s, 3H), 0.69 (s, 3H). MS (ESI) Expected=576; base=594.2 (576+NH4+).

1. additionThe solution was mixed at −10° C. for an additional 12.5 hours
2. customThe layers were separated
3. washthe organic phase was washed with 7% NaHCO3 (2 L)
4. filtrationThe organic phase was filtered
5. concentrationconcentrated under reduced pressure with MTBE (3×200 mL)
6. customto give
7. custom1608.93 g of a very viscous pale-straw colored oil (95.3% potency adjusted yield) that