Methyl iodide → 4-{2-[(3-Bromo-4-chloro-benzoyl)-methyl-amino]-phenyl}-butyric acid methyl ester

HRID 1848594Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[NH:13][C:14](=[O:23])[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Br:22])[CH:16]=1.[H-].[Na+].I[CH3:28]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]([C:14](=[O:23])[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Br:22])[CH:16]=1)[CH3:28]

Participants

Conditions

Temperature: 0 °C

Procedure

To 4-[2-(3-bromo-4-chloro-benzoylamino)-phenyl]-butyric acid methyl ester (1.04 g, 2.54 mmol) in DMF (10 mL) at 0-5° C., was added NaH (152 mg, 3.81 mmol, 60% in mineral oil) in two portions. The mixture was stirred for 15 min at 0° C. and 15 min at rt. After addition of iodomethane (316 μl, 5.08 mmol), the mixture was stirred at room temperature for 12 hrs and was partitioned between ethyl acetate and citric acid. The separated organic layer was then washed with brine and dried over Na2SO4. Concentration and purification by silica gel column chromatography eluting with hexane/ethyl acetate (4/1) up to hexane/ethyl acetate (3/2) yielded 4-{2-[(3-bromo-4-chloro-benzoyl)-methyl-amino]-phenyl}-butyric acid methyl ester (1.0 g). MS [M+H]+: 426.0; tR=2.46 min. (method 1)

Workup

stirringthe mixture was stirred at room temperature for 12 hrs
customwas partitioned between ethyl acetate and citric acid
washThe separated organic layer was then washed with brine
dry with materialdried over Na2SO4
concentrationConcentration and purification by silica gel column chromatography
washeluting with hexane/ethyl acetate (4/1) up to hexane/ethyl acetate (3/2)

Sources & evidence

ORD record: ord-23d8d6a2cf114740ade91fe98d4c3127
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952161B2

Reaction notes

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