Tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate → (4-Methylmorpholin-3-yl)methanol

Temperature

-10 °C

LiAlH4 (4.2 g, 110 mmol) was suspended in anhydrous THF (60 mL) under nitrogen, cooled to −10° C. with stirring and a solution of 3-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (Intermediate 7; 4.1 g, 18.4 mmol) in THF (50 mL) was added dropwise. The reaction mixture was stirred for 20 minutes at 0° C., heated to reflux for 3 h and then stirred at room temperature overnight. The reaction mixture was cooled to −10° C. and quenched with the dropwise addition of 10% water in THF. The reaction mixture was diluted with THF (50 mL), stirred for 1 h at room temperature, filtered and the filtrate was concentrated in vacuo. The residue was dissolved in DCM, dried (MgSO4) and the solvent removed in vacuo to give (4-methyl-morpholin-3-yl)-methanol (2.05 g, 85%) as a colourless liquid.

1. stirringThe reaction mixture was stirred for 20 minutes at 0° C.
2. temperatureheated
3. temperatureto reflux for 3 h
4. stirringstirred at room temperature overnight
5. temperatureThe reaction mixture was cooled to −10° C.
6. customquenched with the dropwise addition of 10% water in THF
7. additionThe reaction mixture was diluted with THF (50 mL)
8. stirringstirred for 1 h at room temperature
9. filtrationfiltered
10. concentrationthe filtrate was concentrated in vacuo
11. dissolutionThe residue was dissolved in DCM
12. dry with materialdried (MgSO4)
13. customthe solvent removed in vacuo

ORD record

ord-7c4f6a66aa3548b187851df43334c972

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07851471B2