Potassium Carbonate → tert-butyl 2,4-difluoro-6-(1-methyl-1H-indol-5-yl)-5-vinylnicotinate

HRID 1481773Notes

Reaction equation

Br[C:2]1[C:3]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([CH3:26])[CH:21]=[CH:20]3)=[N:4][C:5]([F:16])=[C:6]([C:14]=1[F:15])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:27]([B-](F)(F)F)=[CH2:28].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[F:16][C:5]1[N:4]=[C:3]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([CH3:26])[CH:21]=[CH:20]3)[C:2]([CH:27]=[CH2:28])=[C:14]([F:15])[C:6]=1[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of tert-butyl 5-bromo-2,4-difluoro-6-(1-methyl-1H-indol-5-yl)nicotinate (128 mg, 0.30 mmol), potassium vinyltrifluoroborate (80 mg, 0.60 mmol), Pd(OAc)2 (4.7 mg, 0.012 mmol), SPhos (17 mg, 0.024 mmol), aqueous K2CO3 (2.0 M×0.45 mL, 0.9 mmol) and dioxane (2.0 mL) were stirred at 70° C. under Ar overnight. The mixture was cooled and extracted with ethyl acetate. The organic layers were combined, dried, evaporated and purified by silica chromatography (0-5% ethyl acetate in hexanes) to give tert-butyl 2,4-difluoro-6-(1-methyl-1H-indol-5-yl)-5-vinylnicotinate (72 mg, 64%).

Workup

temperatureThe mixture was cooled
extractionextracted with ethyl acetate
customdried
customevaporated
custompurified by silica chromatography (0-5% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-eb51b5630d424fe08f3146dad3a9a264
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409905B2

Reaction notes

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