Hydrochloric Acid → Propanoic acid, 3-((2-methoxy-2-oxoethyl)thio)-, methyl ester

Temperature

45 °C

Methyl thioglycolate (292 g, 2.61 mol) and piperidine (4.43 g, 0.052 mol) were charged to an inerted jacketed reactor equipped with an addition funnel, mechanical stirrer, N2 line and thermocouple thermometer. Methyl acrylate (250 g, 2.87 mol) was then added slowly over a period of 30 min keeping the temperature at approximately 45° C. Upon complete addition, the mixture was stirred at 45° C. for 30 min Piperidine (17.9 g, 210 mmol) was added and stirring at 45° C. continued for 30 min (in order to scavenge of excess acrylate). Tert-butylmethylether (MTBE) (251 ml) was charged, the mixture was cooled to 15° C. and 1 M HCl (251 ml) was added. The mixture was stirred for 5 min and the organic layer was collected and washed with water (251 ml). The mixture was concentrated to a minimum volume by distillation under reduced pressure at 50° C. Dichloromethane (251 ml) was charged and the mixture was again concentrated under reduced pressure by distillation at 40-45° C. Crude product III (480 g) was used in the next step without further purification.

1. customequipped with an addition funnel, mechanical stirrer
2. customat approximately 45° C
3. additionUpon complete addition
4. additionwas added
5. temperaturethe mixture was cooled to 15° C.
6. stirringThe mixture was stirred for 5 min
7. customthe organic layer was collected
8. washwashed with water (251 ml)
9. concentrationThe mixture was concentrated to a minimum volume by distillation under reduced pressure at 50° C
10. additionDichloromethane (251 ml) was charged
11. concentrationthe mixture was again concentrated under reduced pressure by distillation at 40-45° C
12. customCrude product III (480 g) was used in the next step without further purification

ORD record

ord-1d273ce6c2d2467fabec3ba86adb9aaf

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609670B2