Sodium Fluoride → 5-bromo-2-(2,2-difluorocyclopropyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595586Notes

Reaction equation

FS([C:5]([F:14])([F:13])[C:6](O[Si](C)(C)C)=O)(=O)=O.[Br:15][C:16]1[C:17]([N:31]([CH3:36])[S:32]([CH3:35])(=[O:34])=[O:33])=[CH:18][C:19]2[O:23][C:22]([CH:24]=C)=[C:21]([C:26]([NH:28][CH3:29])=[O:27])[C:20]=2[CH:30]=1.[F-].[Na+]>C1(C)C=CC=CC=1.COCCOCCOC>[Br:15][C:16]1[C:17]([N:31]([CH3:36])[S:32]([CH3:35])(=[O:33])=[O:34])=[CH:18][C:19]2[O:23][C:22]([CH:24]3[CH2:6][C:5]3([F:13])[F:14])=[C:21]([C:26]([NH:28][CH3:29])=[O:27])[C:20]=2[CH:30]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of trimethylsilyl 2-fluorosulfonyl-2,2-difluoroacetate (31 mg, 0.12 mmol) in toluene (0.5 mL) was added dropwise to a solution of 5-bromo-N-methyl-6-(N-methylmethylsulfonamido)-2-vinylbenzofuran-3-carboxamide (30 mg, 0.07 mmol) and NaF (1 mg, 0.02 mmol) in diglyme (1 mL) at 120° C. over 15 min. The mixture was then stirred at 120° C. for 2 h. The mixture was concentrated in vacuum and the residue was purified by prep-TLC (PE:EA=1:1) to give the product of 5-bromo-2-(2,2-difluorocyclopropyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (7 mg, yield: 22%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.13 (s, 1H), 8.02 (s, 1H), 3.74˜3.66 (m, 1H), 3.19 (s, 3H), 3.18 (s, 3H), 2.84 (s, 3H), 2.38˜2.39 (m, 1H), 2.21˜2.17 (m, 1H). MS (M+H)+: 437/439.

Workup

concentrationThe mixture was concentrated in vacuum
customthe residue was purified by prep-TLC (PE:EA=1:1)

Sources & evidence

ORD record: ord-9a7a06fee25644c6aebd858da60e55fe
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242998B2

Reaction notes

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