反应详情

温度

70 °C

In an operation carried out in a manner similar to that described in Example 1, 42.3 grams (0.2 mole) of methyldopa, 40.3 milliliters (0.24 mole) of 1-chloroethyl pivalate, 14 grams of 4A molecular sieve pellets (1/16") and 85 milliliters of tetramethylurea are mixed together and heated in an atmosphere of nitrogen to 70° C. and maintained at this temperature for about 30 hours. During this time, the methyldopa dissolves with the formation of (R,S)-1-pivaloyloxyethyl ester product. Thereafter, the reaction mixture is cooled to 25° C. and diluted with 380 milliliters of toluene. The mixture is then washed with three 500 milliliter portions of saturated sodium bicarbonate solution and filtered to clarify the solution. To this solution is added 300 milliliters of isopropanol followed by 16.6 grams (0.14 mole) of 85 percent phosphoric acid and 0.100 gram of methyldopa (R,S)-POE ester phosphoric acid monoisopropanolate seed whereupon the product crystallizes. The crystal-containing slurry is aged for 16 hours at 20°-25° C., then filtered and washed with two 75 milliliter portions of isopropanol and dried in vacuo to obtain (R,S)-1-pivaloyloxyethyl (S)-3-(3,4-dihydroxyphenyl)-2-methylalaninate, phosphoric acid, monoisopropanolate salt.

1. additionare mixed together
2. temperaturemaintained at this temperature for about 30 hours
3. temperatureThereafter, the reaction mixture is cooled to 25° C.
4. washThe mixture is then washed with three 500 milliliter portions of saturated sodium bicarbonate solution
5. filtrationfiltered
6. additionTo this solution is added 300 milliliters of isopropanol
7. customcrystallizes
8. filtrationfiltered
9. washwashed with two 75 milliliter portions of isopropanol
10. customdried in vacuo