Cesium carbonate → methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate

HRID 41169Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[O:8][C:9]3[C:14]([C:15](=[O:17])[CH:16]=2)=[CH:13][C:12]([C:18]([O:20][CH3:21])=[O:19])=[CH:11][C:10]=3[CH:22]2[CH2:26][CH2:25][CH2:24][NH:23]2)[CH2:3][CH2:2]1.Br[C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[F:34][C:32]1[CH:33]=[C:28]([N:23]2[CH2:24][CH2:25][CH2:26][CH:22]2[C:10]2[CH:11]=[C:12]([C:18]([O:20][CH3:21])=[O:19])[CH:13]=[C:14]3[C:9]=2[O:8][C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[CH:16][C:15]3=[O:17])[CH:29]=[C:30]([F:35])[CH:31]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Palladium complex (33 mg, 0.04 mmol, see below) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (270 mg, 0.75 mmol), 1-bromo-3,5-difluorobenzene (0.095 ml, 0.83 mmol) and cesium carbonate (368 mg, 1.13 mmol) dissolved in 1,4-dioxane (5 mL). The resulting suspension was degassed with argon and then stirred at 80° C. for 23 h. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 6% MeOH in EtAc. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (206 mg, 58%) as a clear yellow foam.

Workup

customThe resulting suspension was degassed with argon
temperatureto cool to room temperature
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 6% MeOH in EtAc
customThe solvent was evaporated to dryness

Sources & evidence

ORD record: ord-60e44a26519f419db7b74f7c8a9c59d3
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530470B2

Reaction notes

Loading…