4-Methylmorpholine → 2-(4-Dimethylamino-phenyl)-N-methoxy-N-methyl-acetamide

HRID 2388979Notes

Reaction equation

[CH3:1][N:2]([CH3:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](O)=[O:11])=[CH:5][CH:4]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.Cl.[CH3:33][NH:34][O:35][CH3:36]>O1CCCC1>[CH3:1][N:2]([CH3:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([N:34]([O:35][CH3:36])[CH3:33])=[O:11])=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a 0° C. mixture of 4-(dimethylamino)phenylacetic acid (4.91 g, 27.40 mmol) in tetrahydrofuran (150 ml), were added 2-chloro-4,6-dimethoxy-1,3,5-triazine (5.05 g, 28.76 mmol) and 4-methylmorpholine (9.6 ml, 87.32 mmol). The reaction mixture was stirred for 1 hour at 0° C. N,O-dimethylhydroxylamine hydrochloride (5.35 g, 54.84 mmol) was added and stirred for 18 hours at room temperature. The reaction was quenched with saturated ammonium chloride solution, and extracted with methylene chloride. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (0 to 40% ethyl acetate in hexanes) to give 2.76 g (45%) of 2-(4-dimethylamino-phenyl)-N-methoxy-N-methyl-acetamide. 1H NMR (250 MHz, CDCl3) δ 7.15 (d, J=8.7 Hz, 2H), 6.67 (s, J=8.7 Hz, 2H), 3.65 (s, 2H), 3.58 (s, 3H), 3.16 (s, 3H), 2.89 (s, 6H).

Workup

stirringstirred for 18 hours at room temperature
customThe reaction was quenched with saturated ammonium chloride solution
extractionextracted with methylene chloride
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was purified by flash chromatography (0 to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-aacdf8b1cdd44425be39c4e26ce5a739
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08268994B2

Reaction notes

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