tert-Butyl (2S)-2-(hydroxymethyl)morpholine-4-carboxylate → (S)-4-Methyl-2-(hydroxymethyl)morpholine

(S)-2-Hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (Intermediate 8; 1.20 g, 5.52 mmol) in THF (5 mL) was added to a suspension of LiAlH4 (1.30 g, 34.3 mmol) in anhydrous THF (15 mL) at −10° C. and stirred under nitrogen for 15 min. The cooling bath was removed and the reaction mixture was gently heated to reflux for 4 h. The reaction mixture was quenched by careful addition of a mixture of water (4 mL) in THF (25 mL) with ice bath cooling. THF (50 mL) was added to the reaction mixture, stirred for 15 min, filtered and the solid washed with THF (50 mL). The combined filtrates were evaporated in vacuo. The residue was dissolved in DCM (50 mL), dried (MgSO4) and the solvent removed in vacuo to give (S)-(4-methylmorpholin-2-yl)-methanol (490 mg, 67%) as a colourless oil.

1. customThe cooling bath was removed
2. temperaturethe reaction mixture was gently heated
3. temperatureto reflux for 4 h
4. customThe reaction mixture was quenched by careful addition of a mixture of water (4 mL) in THF (25 mL) with ice bath
5. temperaturecooling
6. additionTHF (50 mL) was added to the reaction mixture
7. stirringstirred for 15 min
8. filtrationfiltered
9. washthe solid washed with THF (50 mL)
10. customThe combined filtrates were evaporated in vacuo
11. dissolutionThe residue was dissolved in DCM (50 mL)
12. dry with materialdried (MgSO4)
13. customthe solvent removed in vacuo

ORD record

ord-d5881dd35c25465d88aa35c4ebf6d480

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07851471B2