Cesium carbonate → methyl 2-((S)-6-((2',6'-dimethyl-4'-(((R)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 2280653Notes

Reaction equation

CS([O:5][C@H:6]1[CH2:10][CH2:9][N:8]([S:11]([CH3:14])(=[O:13])=[O:12])[CH2:7]1)(=O)=O.O[C:16]1[CH:21]=[C:20]([CH3:22])[C:19]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][O:30][C:31]3[CH:44]=[CH:43][C:34]4[C@H:35]([CH2:38][C:39]([O:41][CH3:42])=[O:40])[CH2:36][O:37][C:33]=4[CH:32]=3)[CH:24]=2)=[C:18]([CH3:45])[CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:45][C:18]1[CH:17]=[C:16]([O:5][C@@H:6]2[CH2:10][CH2:9][N:8]([S:11]([CH3:14])(=[O:13])=[O:12])[CH2:7]2)[CH:21]=[C:20]([CH3:22])[C:19]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][O:30][C:31]2[CH:44]=[CH:43][C:34]3[C@H:35]([CH2:38][C:39]([O:41][CH3:42])=[O:40])[CH2:36][O:37][C:33]=3[CH:32]=2)[CH:24]=1

Participants

Conditions

Temperature: 80 °C

Procedure

(s)-1-(Methylsulfonyl)pyrrolidin-3-yl methanesulfonate 11c (41 mg, 0.17 mmol), (S)-methyl 2-(6-((4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 3 h (70 mg, 0.17 mmol) and cesium carbonate (165 mg, 0.50 mmol) were dissolved in 10 mL of N,N-dimethylformamide. The reaction solution was heated to 80° C., and stirred for 12 hours. The resulting solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography with elution system B to obtain the title compound methyl 2-((S)-6-((2′,6′-dimethyl-4′-(((R)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 11d (71 mg, yield 75.1%) as a light yellow slime.

Workup

concentrationThe resulting solution was concentrated under reduced pressure
customthe residue was purified by silica gel column chromatography with elution system B

Sources & evidence

ORD record: ord-3963fff9110f44e2ae146a87445edffc
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139548B2

Reaction notes

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