Dimethylformamide → 3-[6-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indol-1-yl]-propionic acid ethyl ester

HRID 551503Notes

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]=[C:24]4[C:20]([CH:21]=[CH:22][NH:23]4)=[CH:19][CH:18]=3)=[CH:11][CH:10]=2)=[C:4]([O:26][CH3:27])[CH:3]=1.CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:39]([O:41][C:42](=[O:46])[CH2:43][CH2:44]Br)[CH3:40]>CS(C)=O>[CH2:39]([O:41][C:42](=[O:46])[CH2:43][CH2:44][N:23]1[C:24]2[C:20](=[CH:19][CH:18]=[C:17]([CH2:16][O:15][C:12]3[CH:13]=[CH:14][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:10][CH:11]=3)[CH:25]=2)[CH:21]=[CH:22]1)[CH3:40]

Participants

Conditions

Temperature: 90 °C

Procedure

To 6-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-1H-indole (37 mg, 0.10 mmol, 1 eq.) was added dimethylformamide (1 mL), cesium carbonate (40 mg, 0.11 mmol, 1.1 eq.) and 3-bromo-propionic acid ethyl ester (0.014 mL, 0.11 mmol, 1.1 eq.). The reaction was stirred and heated at 90° C. for 17 hr. The reaction was diluted with dimethylsulfoxide, filtered, and purified by HPLC with a 50-100% acetonitrile in water gradient to yield 3-[6-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-indol-1-yl]-propionic acid ethyl ester as clear oil (33 mg, 73%). LC-MS (ES) calculated for C27H25F2NO4, 465.2; found m/z 466 [M+H]+.

Workup

filtrationfiltered
custompurified by HPLC with a 50-100% acetonitrile in water gradient

Sources & evidence

ORD record: ord-c525f872298f44b5bd7f32d26acefdfd
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947728B1

Reaction notes

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