Chloromethyl ethyl ether → 1-ethoxymethyl-5-methoxy-3-(1-methylethoxy)-1H-indole-2-carboxamide

HRID 21600

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([NH2:14])=[O:13])=[C:6]2[O:15][CH:16]([CH3:18])[CH3:17].[H-].[Na+].[CH2:21]([O:23][CH2:24]Cl)[CH3:22]>CN(C)C=O.CCCCCC>[CH2:21]([O:23][CH2:24][N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[C:6]([O:15][CH:16]([CH3:18])[CH3:17])=[C:7]1[C:12]([NH2:14])=[O:13])[CH3:22]

Participants

Conditions

Temperature: 0 °C

Procedure

5-Methoxy-3-(1-methylethoxy)-1H-indole-2-carboxamide (328 mg, 1.32 mmol) in 5 mL of dimethylformamide is added to a suspension of sodium hydride (60% by weight) (67 mg, 1.67 mol) in 5 mL of dimethylformamide. After 1.5 hours the mixture is cooled to 0° C. and chloromethyl ethyl ether (160 μL, 1.72 mmol) is added dropwise, and the solution is stirred at 0° C. for 20 minutes and then at room temperature for 1.5 hours. The reaction mixture is diluted with 1:1 hexane:ethyl acetate and washed with brine. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo. Chromatography eluting with 1:1 ethyl acetate:hexane gives 240 mg (51%) of 1-ethoxymethyl-5-methoxy-3-(1-methylethoxy)-1H-indole-2-carboxamide; mp 110°-112° C.

Workup

waitat room temperature for 1.5 hours
washethyl acetate and washed with brine
dry with materialThe organic layer is dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
washChromatography eluting with 1:1 ethyl acetate

Sources & evidence

ORD record: ord-859a8129a115414292c81e086605f598
Source dataset: uspto-grants-1995_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05424329

Linked notes

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