Ethyl Acetate → 3-[4-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acid ethyl ester

HRID 551495Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[N:20][NH:21]4)=[CH:11][CH:10]=2)=[C:4]([O:26][CH3:27])[CH:3]=1.Br[CH:29]([CH3:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31].C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C.O>[CH2:33]([O:32][C:30](=[O:31])[CH2:29][CH2:35][N:21]1[C:22]2[C:18](=[C:17]([CH2:16][O:15][C:12]3[CH:11]=[CH:10][C:9]([C:5]4[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=4[O:26][CH3:27])=[CH:14][CH:13]=3)[CH:25]=[CH:24][CH:23]=2)[CH:19]=[N:20]1)[CH3:34]

Participants

Conditions

Temperature: 90 °C

Procedure

4-(4′,5′-Difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-1H-indazole (0.09 g, 0.245 mmol), ethyl bromopropionate (0.045 g, 0.245 mmol), cesium carbonate (81 mg, 0.294 mmol) in 6 mL DMF was stirred at RT overnight and then heated to 90° C. for 35 min. The reaction was cooled and distributed between EtOAc and H2O. The organic layer was separated and concentrated in vacuo. The crude product was purified by flash chromatography with a gradient from 0-30% ethyl acetate in hexanes to yield 3-[4-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acid ethyl ester as a white solid (98 mg, 85.7%).

Workup

temperatureThe reaction was cooled
customThe organic layer was separated
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography with a gradient from 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-7ac90e32f2534afb8fb10579fcfc86d0
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947728B1

Reaction notes

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