Hydrochloric Acid → Methyl 3-acetyl-5-((1-(4-fluorophenyl)ethyl)-carbamoyl)benzoate

HRID 1454210Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12](=[O:23])[NH:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH3:15])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH:24]([O:26]CCCC)=[CH2:25].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:24]([C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12](=[O:23])[NH:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH3:15])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])(=[O:26])[CH3:25]

Participants

Conditions

Temperature: 122 °C

Procedure

A mixture of methyl 3-bromo-5-((1-(4-fluorophenyl)ethyl)-carbamoyl)benzoate (880 mg, 2.32 mmol), 1-(vinyloxy)butane (464.7 mg, 0.6 mL, 4.64 mmol), palladium acetate (16.0 mg, 0.070 mmol), DPPP (63.1 mg, 0.0153 mmol) and potassium carbonate (382 mg, 2.78 mmol) in DMF (2.5 mL) and H2O (0.3 mL) in a Smith process vial was heated at 122° C. in microwave for 3 h. The reaction mixture was cooled down to RT and hydrolyzed by addition of 5% HCl slowly. The reaction mixture was worked up by extraction with ethyl acetate and concentration under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (520 mg, 65.4% yield): HPLC retention time: 1.88 min (method A). MS (ESI) (M+H)+ 343.00.

Workup

extractionThe reaction mixture was worked up by extraction with ethyl acetate and concentration under vacuum
customThe crude mixture was purified by reverse phase prep HPLC

Sources & evidence

ORD record: ord-4b2bb2f369af442b803081ec5df242f7
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07476764B2

Reaction notes

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