Cesium carbonate → methyl 2-(4-fluorophenyl)-6-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carboxylate

HRID 1890271Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[N:20][N:21]2[C:25](=O)[CH2:24][CH2:23][CH:22]2[CH3:27])[CH2:15][C:16]([O:18][CH3:19])=[O:17])=[CH:10][CH:9]=1.C(OCC)(=O)C.O>CN(C)C=O>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:25]3[CH2:24][CH2:23][CH:22]([CH3:27])[N:21]3[N:20]=2)=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

23.2 g (71.2 mmol) of caesium carbonate are added to a solution of 10.4 g (35.6 mmol) of methyl 3-(4-fluorophenyl)-3-[(2-methyl-5-oxopyrrolidin-1-yl)imino]propanoate in 100 ml of dimethylformamide. The reaction mixture is stirred at room temperature for 30 min and at 100° C. for 4 h. Ethyl acetate/water is then added, the organic phase separated off and the aqueous phase is extracted with 3×100 ml of ethyl acetate. The combined organic phases are dried over Na2SO4 and freed from the solvent under reduced pressure. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate) gives 6.6 g (64%) of the desired product; log P(HCOOH): 2.84; 1H-NMR (ppm): δ (DMSO-d6)=1.44 (d, 3H), 2.14-2.17 (m, 1H), 2.76-2.78 (m, 1H), 2.98-3.08 (m, 2H), 3.68 (s, 3H), 4.46 (m, 1H), 7.21-7.24 (m, 2H), 7.73-7.76 (m, 2H); LC-MS: m/z=275 [M+H]+.

Workup

customthe organic phase separated off
extractionthe aqueous phase is extracted with 3×100 ml of ethyl acetate
dry with materialThe combined organic phases are dried over Na2SO4
customPurification by column chromatography on silica gel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record: ord-ace517bdf2904e209b293e5bad61618f
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507472B2

Reaction notes

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