反应详情

A reactor is charged with 3-amino-1-morpholin-4-yl-propan-1-one; hydrochloride (765 mmol). MeOH (380 mL) is added, and the mixture is stirred vigorously at room temperature for ca. 10 minutes. MtBE (380 mL) is added and the resulting slurry is cooled to −10° C., where a 25% (w/w) MeOH solution of NaOMe (765 mmol) is added slowly via addition funnel at such a rate as to maintain an internal temperature of ca. −10° C. The resulting suspension is stirred vigorously under a N2 atmosphere as it is allowed to warm to 0° C. Solids are removed via filtration, rinsing with additional MtBE (50 mL). Solvent is removed in vacuo to provide the free base as a crude oil that is taken up in MtBE (600 mL). The mixture is cooled with vigorous agitation to ca. 0° C., where phenylacetic acid (765 mmol) is added slowly as a solution in MtBE (300 mL). The reaction mixture is stirred an additional 10 minutes after complete addition, during which time the product precipitates out of solution. The solids are collected via filtration, washed with additional MtBE (100 mL) and dried under vacuum at ≦40° C. to provide 3-amino-1-morpholin-4-yl-propan-1-one; compound with phenylacetic acid (191 g). This material is carried on to subsequent steps without further purification, or optionally, it can be re-precipitated from MtBE.

1. additionMtBE (380 mL) is added
2. temperaturethe resulting slurry is cooled to −10° C.
3. temperatureto maintain an internal temperature of ca. −10° C
4. stirringThe resulting suspension is stirred vigorously under a N2 atmosphere as it
5. temperatureto warm to 0° C
6. customSolids are removed via filtration
7. washrinsing with additional MtBE (50 mL)
8. customSolvent is removed in vacuo
9. customto provide the free base as a crude oil that
10. temperatureThe mixture is cooled with vigorous agitation to ca. 0° C.
11. stirringThe reaction mixture is stirred an additional 10 minutes
12. additionafter complete addition
13. customduring which time the product precipitates out of solution
14. filtrationThe solids are collected via filtration
15. washwashed with additional MtBE (100 mL)
16. customdried under vacuum at ≦40° C.