Cesium carbonate → 5-Bromo-4-chloro-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-benzoic acid methyl ester

HRID 2353909Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([Br:10])[C:7]([Cl:11])=[CH:6][C:5]=1[NH:12][C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:27][CH2:28][CH2:29][C:30]([O:32][CH3:33])=[O:31]>CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([Br:10])[C:7]([Cl:11])=[CH:6][C:5]=1[N:12]([C:13]([O:15][CH:16]([CH3:17])[CH3:18])=[O:14])[CH2:27][CH2:28][CH2:29][C:30]([O:32][CH3:33])=[O:31]

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 5-Bromo-4-chloro-2-isopropoxycarbonylamino-benzoic acid methyl ester (2.52 g, 7.19 mmol) and cesium carbonate (4.68 g, 14.4 mmol) in DMF (35 ml) under nitrogen was added methyl 4-bromobutyrate (2.60 g, 14.4 mmol) dropwise. The reaction mixture was heated to 60° C. for 4 hours and then cooled to room temperature. The mixture was diluted with ethyl acetate (100 ml), and then washed with 0.1N HCl(aq) (100 ml) and brine (3×100 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (gradient eluent, 0-20% ethyl acetate in hexane) provided 5-Bromo-4-chloro-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-benzoic acid methyl ester (2.78 g, 86%) as oil. MS (ES+): 450, 452 (M+H).

Workup

temperaturecooled to room temperature
washwashed with 0.1N HCl(aq) (100 ml) and brine (3×100 ml)
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated under reduced pressure
customPurification by silica gel chromatography (gradient eluent, 0-20% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-d1ccd342c2bf4ee181ee2c7e7026a2bc
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07749992B2

Reaction notes

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