Chloroacetyl chloride → (R)-4-Benzyl-5-oxo-3-morpholinecarboxylic Acid

Temperature

-10 °C

K2CO3 (10.6 g, 76.4 mmol) in H2O (30 mL) precooled to 0° C. was added to N-(phenylmethyl)-D-serine (4.91 g, 25.2 mmol) in THF (30 mL) cooled to −10° C., internal temperature. Chloroacetyl chloride (3.30 mL, 41.4 mmol) was added dropwise, keeping the internal temperature below 5° C. After stirring for 2 h NaOH (10 mL, 50% w/w in water), precooled to 0° C. was added dropwise, keeping the internal temperature below 10° C. The reaction mixture was stirred for 2 h and subsequently warmed to rt. The reaction mixture was washed twice with heptane (20 mL) and the aqueous layer was cooled to −5° C. Concentrated HCl was added until pH <2, keeping the internal temperature below 10° C. The mixture was placed in a freezer overnight and the solid was filtered, washed twice with cold H2O (20 mL) and dried at 50° C. in a vacuum oven to give the title compound of step B (3.67 g, 15.6 mmol, 62%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.78 (d, J=15.4 Hz, 1H), 3.84-3.92 (m, 2H), 4.05-4.15 (m, 3H), 5.21 (d, J=15.2 Hz, 1H), 7.20-7.31 (m, 5H), 13.20 (br. s., 1H). [α]D20° C.=−108.6, I=100 mm, c=1.0 in 1N NaOH.

1. customprecooled to 0° C.
2. customthe internal temperature below 5° C
3. customprecooled to 0° C.
4. additionwas added dropwise
5. customthe internal temperature below 10° C
6. temperaturesubsequently warmed to rt
7. washThe reaction mixture was washed twice with heptane (20 mL)
8. temperaturethe aqueous layer was cooled to −5° C
9. additionConcentrated HCl was added until pH <2
10. customthe internal temperature below 10° C
11. waitThe mixture was placed in a freezer overnight
12. filtrationthe solid was filtered
13. washwashed twice with cold H2O (20 mL)
14. customdried at 50° C. in a vacuum oven

ORD record

ord-b5d17e81ba334d6fa7b319429027bbbe

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093239B2