Cesium carbonate → 1-t-Butyl 2-methyl (2S,4R)-4-[(2-bromo-6-methoxyquinolin-3-yl)oxy]pyrrolidine-1,2-dicarboxylate

HRID 2045718Notes

Reaction equation

C([O-])([O-])=O.[Cs+].[Cs+].BrC1C=CC(S([O:17][C@@H:18]2[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:20]([C:30]([O:32][CH3:33])=[O:31])[CH2:19]2)(=O)=O)=CC=1.[Br:34][C:35]1[C:44](O)=[CH:43][C:42]2[C:37](=[CH:38][CH:39]=[C:40]([O:46][CH3:47])[CH:41]=2)[N:36]=1>CN1C(=O)CCC1.CCOC(C)=O>[Br:34][C:35]1[C:44]([O:17][C@H:18]2[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[C@H:20]([C:30]([O:32][CH3:33])=[O:31])[CH2:19]2)=[CH:43][C:42]2[C:37](=[CH:38][CH:39]=[C:40]([O:46][CH3:47])[CH:41]=2)[N:36]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Cs2CO3 (10.7 g, 32.9 mmol) was added to a stirred mixture of 1-tert-butyl 2-methyl (2S,4S)-4-{[(4-bromophenyl)sulfonyl]oxy}pyrrolidine-1,2-dicarboxylate (8.78 g, 18.9 mmol) and 2-bromo-6-methoxyquinolin-3-ol (4.18 g, 16.45 mmol) in NMP (46 mL). The resulting mixture was stirred at 50° C. for 3 h, then cooled and diluted with EtOAc. The organics were washed with saturated aqueous NaHCO3, water and brine then dried over Na2SO4. Filtration and removal of the volatiles gave a residue, which was purified by column chromatography on silica gel (gradient elution: 1 to 100% EtOAc in petroleum ether) to give the title compound (5.56 g, 70.2%). LCMS (ES+) m/z 481, 483 (M+H)+.

Workup

temperaturecooled
washThe organics were washed with saturated aqueous NaHCO3, water and brine
dry with materialthen dried over Na2SO4
filtrationFiltration and removal of the volatiles
customgave a residue, which
customwas purified by column chromatography on silica gel (gradient elution: 1 to 100% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-4d2d88a020944b7f974769539c1ff711
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08591878B2

Reaction notes

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