Methyl iodide → 4-[(tert-Butoxycarbonyl-methyl-amino)-methyl]-3-methyl-benzoic acid methyl ester

HRID 2355278Notes

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5](=[O:22])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:8]([CH3:21])[CH:7]=1.[CH3:23]I>CN(C)C=O>[CH3:3][O:4][C:5](=[O:22])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH3:23])=[C:8]([CH3:21])[CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Add in portions of 60% sodium hydride dispersion in oil (472 mg, 11.81 mmol) to 4-(tert-butoxycarbonylamino-methyl)-3-methyl-benzoic acid methyl ester (3.0 g, 10.74 mmol) in anhydrous dimethylformamide (50 mL) at 0° C. under argon gas. After complete addition, stir the reaction mixture for 15 min at 0° C. Add methyl iodide (735 μL, 11.8 mmol) to the reaction mixture. Allow the reaction mixture to warm-up to room temperature and stir overnight. Quench the reaction mixture with saturated aqueous ammonium chloride and extract with ethyl acetate (3×). Combine the organic layers, wash with brine, dry over sodium sulfate, and concentrate. Purify the residue by chromatography (silica gel) eluting with 25% ethyl acetate/hexane to give the title compound. MS (m/z): 316 (M+23).

Workup

additionAfter complete addition
temperatureto warm-up to room temperature
stirringstir overnight
customQuench the reaction mixture with saturated aqueous ammonium chloride
extractionextract with ethyl acetate (3×)
washCombine the organic layers, wash with brine
dry with materialdry over sodium sulfate
concentrationconcentrate
customPurify the residue by chromatography (silica gel)
washeluting with 25% ethyl acetate/hexane

Sources & evidence

ORD record: ord-7a57eb338d234a67ba3240260666c83a
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754742B2

Reaction notes

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