Methanol → Methyl 2,2,2-trimethoxyacetate

A 500 mL round bottom flask was charged with methyl 2,2-dichloro-2-methoxyacetate (50 g, 248.5 mmol, 1 equiv). This was cooled to 0° C. with an ice bath at which point anhydrous methanol (34.33 g, 745.7 mmol, 44 mL, 3 equiv) was added with stirring over the course of 5 minutes. The mixture was then immediately diluted with anhydrous diethyl ether (150 mL). While maintaining the reaction at 0° C. with an external ice bath, anhydrous pyridine (49.10 g, 621.4 mmol, 50.20 mL, 2.5 equiv) was added via a pressure equalizing addition funnel over 1 hour. The reaction mixture was then rapidly stirred for an additional 30 minutes at 0° C. The stirring was then stopped and the mixture allowed to stand at room temperature for 72 hours where upon long white needles were formed in solution. The resulting mixture was filtered through a medium porosity glass frit, and the recovered solids were washed with diethyl ether. The filtrate was then concentrated by rotary evaporation under reduced pressure to yield a pale yellow oil. This oil was subsequently cooled to 0° C. with an ice bath. The oil was then rapidly stirred, and pyrrolidine (25 mL) was added in a drop wise fashion, by means of a pressure equalizing addition funnel, over a period of 20 minutes. The solution rapidly turned yellowish-orange in color. Upon completion of addition of the pyrrolidine, the mixture was stirred for an additional 30 minutes at 0° C., and then subjected to a reduced pressure distillation collecting unreacted pyrrolidine and ethanol at 40 Torr and 28° C. followed by the desired material, methyl 2,2,2-trimethoxyacetate (44 g, 80% yield) at 2 Torr and 58° C., as a colorless liquid.

1. additionwas added
2. temperatureWhile maintaining
3. customthe reaction at 0° C. with an external ice bath
4. additionaddition funnel over 1 hour
5. stirringThe reaction mixture was then rapidly stirred for an additional 30 minutes at 0° C
6. waitto stand at room temperature for 72 hours
7. customwhere upon long white needles were formed in solution
8. filtrationThe resulting mixture was filtered through a medium porosity glass frit
9. washthe recovered solids were washed with diethyl ether
10. concentrationThe filtrate was then concentrated by rotary evaporation under reduced pressure
11. customto yield a pale yellow oil
12. stirringThe oil was then rapidly stirred
13. additionaddition funnel
14. waitover a period of 20 minutes
15. stirringthe mixture was stirred for an additional 30 minutes at 0° C.
16. distillationsubjected to a reduced pressure distillation
17. customcollecting unreacted pyrrolidine and ethanol at 40 Torr and 28° C.

ORDレコード

ord-7304e492f0604a488b8b1a092bcf9e75

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09346807B2