Methyl iodide → 4-tert-Butyl 2-methyl morpholine-2,4-dicarboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O.O>[CH3:17][O:15][C:14]([CH:10]1[O:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)=[O:16]Participants
Procedure
A solution of morpholine-2,4-dicarboxylic acid 4-tert-butyl ester (supplied by NeoMPS, Inc.), (5.78 g, 25.0 mmol) in N,N-dimethylformamide (30 mL) was subsequently treated with potassium carbonate (4.14 g, 30.0 mmol) and iodomethane (7.10 g, 3.1 mL, 50.0 mmol). After stirring at room temperature for 18 h, the reaction mixture was diluted with water and the aqueous layer was extracted with ethyl acetate. The organic extracts were combined, washed with water (4×) and brine then filtered through a hydrophobic frit and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 3:1 to 1:3 to afford the title compound (4.83 g, 79%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 3.06-3.15 (m, 2H), 3.56-3.64 (m, 1H), 3.75-3.79 (m, 1H), 3.81 (s, 3H), 4.00-4.14 (m, 3H). LCMS (m/z) 268.1 [M+Na], Tr=1.94 min.
Workup
- extractionthe aqueous layer was extracted with ethyl acetate
- washwashed with water (4×) and brine
- filtrationthen filtered through a hydrophobic frit
- customthe volatiles were removed in vacuo
- customThe residue was purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-81021edb0b8245f9a3069e3e1a8e626d
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09062092B2
Reaction notes
Loading…