Cesium fluoride → tert-butyl 4a-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo-[4,5-b]pyridin-5-yl]-4,4-difluorooctahydro-2H-cyclopropa[3,4]cyclopenta[1,2-c]pyrrole-2-carboxylate

HRID 629901Notes

Reaction equation

[CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C:13]3[CH2:14][CH:15]4[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17][CH:16]4[CH:27]=3)=[CH:10][CH:11]=2)[N:6]([CH3:28])[C:5]1=[O:29].[F-].[Cs+].[F:34][C:35]([F:47])(S(F)(=O)=O)C(O[Si](C)(C)C)=O>C1(C)C=CC=CC=1>[CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C:13]34[C:35]([F:47])([F:34])[CH:27]3[CH:16]3[CH2:17][N:18]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:19][CH:15]3[CH2:14]4)=[CH:10][CH:11]=2)[N:6]([CH3:28])[C:5]1=[O:29]

Participants

Conditions

Temperature: 100 °C

Procedure

tert-Butyl 5-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]-3,3a,4,6a-tetrahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (8-3, 73 mg, 0.17 mmol, 1.0 equiv) and cesium fluoride (2.6 mg, 0.02 mmol, 0.1 equiv) were added to anhydrous toluene (428 μL) and the resulting mixture was placed in a 100° C. bath. A solution of trimethylsilyl difluoro(fluorosulfonyl)acetate (30-1, 176 mg, 0.70 mmol, 4.1 equiv) in anhydrous toluene (1.3 mL) was then added dropwise via syringe pump over a period of 8 h. After stirring at 100° C. for an additional 6 h, the contents were filtered through Celite and purified by reverse-phase HPLC (40-100% 0.1% TFA in H2O:CH3CN) to give 30-2 as a colorless semi-solid. MS m/z (M+H): calculated=509.1276; observed=509.1278.

Workup

customwas placed in a 100° C.
filtrationthe contents were filtered through Celite
custompurified by reverse-phase HPLC (40-100% 0.1% TFA in H2O:CH3CN)

Sources & evidence

ORD record: ord-d9dcf947f4d44cb7a2f3162f1742eb6a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315518B2

Reaction notes

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