4-Methylmorpholine → Morpholine-4-carboxamide

Temperature

20 °C

To a solution of (3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carboxylic acid (5.0 g, 24.5 mmol) in THF (100 mL, 20×) was added TBTU (11.8 g, 1.5 equiv), N-methylmorpholine (NMM, 4.1 mL, 1.5 equiv) and the mixture was stirred at 20° C. for 30 min. Morpholine (3.2 mL, 1.5 equiv) was then added, and the reaction mixture was stirred at 20° C. for an additional 6 h. The solid was filtered off by filtration and the cake was washed with THF (10 mL, 2× x2). The organic solution was concentrated under vacuum and the residue was purified by silica gel column chromatography (hexanes:EtOAc, from 1:4 to 4:1) to afford 4.3 g of the desired morpholine amide (64%) as a white solid. 1H NMR (CDCl3), δ 6.02 (d, J=3.2 Hz, 1H), 5.11 (br s, 1H), 4.62 (d, J=3.2 Hz, 1H), 4.58 (d, J=3.2 Hz, 1H), 3.9-3.5 (m, 8H), 1.51 (s, 3H), 1.35 (s, 3H).

1. stirringthe reaction mixture was stirred at 20° C. for an additional 6 h
2. filtrationThe solid was filtered off by filtration
3. washthe cake was washed with THF (10 mL, 2× x2)
4. concentrationThe organic solution was concentrated under vacuum
5. customthe residue was purified by silica gel column chromatography (hexanes:EtOAc, from 1:4 to 4:1)

ORD record

ord-af0f06d3286d42fbb04ff1f1c8c6a9f3

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293878B2