Morpholine → 4-Morpholineacetic acid, 1,1-dimethylethyl ester

Temperature

60 °C

To a stirred solution of tert-butyl bromoacetate (8.47 mL, 57.4 mmol) in THF (50 mL) was added a 1:1 mixture of triethylamine (8 mL, 57.4 mmol) and morpholine (5.02 mL, 57.4 mmol), dropwise (a mild exotherm was observed) and the resulting white suspension was stirred at 60° C. for 2 h. The mixture was diluted with water (100 mL) and saturated sodium carbonate (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated then chromatographed in 0%-100% ethyl acetate in hexanes. Product-containing fractions were concentrated in vacuo giving the title product (11.5 g, quantitative) as a pale yellow liquid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 3.78-3.71 (m, 4H), 3.10 (s, 2H), 2.59-2.54 (m, 4H), 1.46 (m, 9H).

1. extractionextracted with ethyl acetate (2×50 mL)
2. washThe combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL)
3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customthen chromatographed in 0%-100% ethyl acetate in hexanes
7. concentrationProduct-containing fractions were concentrated in vacuo

ORD record

ord-5c32a4b1253d4a859f8e233b724e9d5a

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09441012B2