Cesium carbonate → 1-[2-(4-tert-butyl-phenyl)-2-oxo-ethyl]-4-fluoro-1H-pyrrole-2-carboxylic acid methyl ester

HRID 2272965Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([F:10])[CH:9]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:23][CH:22]=1)=[O:20]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:23][CH:22]=2)=[O:20])[CH:7]=[C:8]([F:10])[CH:9]=1)=[O:4]

Participants

Conditions

Temperature: 50 °C

Procedure

A suspension of 93.7 mg (0.655 mmol) 4-fluoro-1H-pyrrole-2-carboxylic acid methyl ester (synthesis described in J. Leroy et al. Tetrahedron 58, p. 6713, 2002) and 640 mg (1.96 mmol) cesium carbonate in 1.3 ml DMF is heated to 50° C. under stirring. 167 mg (0.655 mmol) 2-bromo-1-(4-tert-butyl-phenyl)ethanone is added and the reaction mixture is stirred for 18 hours at 50° C. The reaction mixture is filtered with suction and the filtrate is evaporated. The residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent to give 1-[2-(4-tert-butyl-phenyl)-2-oxo-ethyl]-4-fluoro-1H-pyrrole-2-carboxylic acid methyl ester as brown amorphous solid; HPLC/MS 3.26 min (B), [M+H] 318.

Workup

stirringthe reaction mixture is stirred for 18 hours at 50° C
filtrationThe reaction mixture is filtered with suction
customthe filtrate is evaporated
customThe residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent

Sources & evidence

ORD record: ord-b387f023f7614cdb9e5128b9f9fc5b50
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120805B2

Reaction notes

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