Cesium fluoride → HCID 86722450, compound

HRID 718844Notes

Reaction equation

HRID 718844 reaction equation
[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C@@:18]3([C:28]#[N:29])[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][C@@H:19]3[CH2:20][CH2:21][O:22][C:3]=12.[Br:30][C:31]1[C:39]2[N:38]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)[N:37]=[CH:36][C:35]=2[CH:34]=[C:33]2[C@:47]3([C:57]#[N:58])[CH2:55][CH2:54][C:53](=[O:56])[CH2:52][C@H:48]3[CH2:49][CH2:50][O:51][C:32]=12.[F-].[Cs+].[F:61][C:62]([Si](C)(C)C)([F:64])[F:63].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CCOC(C)=O.O.COCCOC>[Br:1][C:2]1[C:10]2[N:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C@@:18]3([C:28]#[N:29])[CH2:26][CH2:25][C@@:24]([OH:27])([C:62]([F:64])([F:63])[F:61])[CH2:23][C@@H:19]3[CH2:20][CH2:21][O:22][C:3]=12.[Br:30][C:31]1[C:39]2[N:38]([C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)[N:37]=[CH:36][C:35]=2[CH:34]=[C:33]2[C@:47]3([C:57]#[N:58])[CH2:55][CH2:54][C@:53]([OH:56])([C:62]([F:64])([F:63])[F:61])[CH2:52][C@H:48]3[CH2:49][CH2:50][O:51][C:32]=12

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilane2×HCID 2724141Tetrabutylammonium FluorideHCID 86722452HCID 86722452, compound

Product 1

HCID 86722450HCID 86722450, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

DME (40.0 mL) was added to a mixture of (4aR,12bS)-8-bromo-9-(4-fluorophenyl)-3-oxo-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile; compound with (4aS,12bR)-8-bromo-9-(4-fluorophenyl)-3-oxo-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile (104, R1=4-Fluorophenyl) and CsF (0.060 g, 0.40 mmol) under a nitrogen atmosphere. After about 15 min, the reaction mixture was cooled to about 0° C. (Trifluoromethyl)trimethylsilane (0.720 mL, 4.87 mmol) was added dropwise over about 5 min. After about 2 h, (trifluoromethyl)trimethylsilane (0.250 mL, 1.69 mmol) was added dropwise. After about 2 h, the volatiles were removed under reduced pressure. The residue was dissolved in THF (40.0 mL). TBAF (1 M solution in THF, 5.00 mL, 5.00 mmol) was added. After about 1 h, the solution was diluted with EtOAc (100 mL) and water (50 mL). The layers were separated and the organic layer was washed with aq. NaCl (50 mL) then dried over Na2SO4, filtered and concentrated under reduced pressure. DCM (5 mL) was added and the solid was collected by filtration rinsing with DCM (2×2 mL) and dried under reduced pressure to afford (3R,4aR,12bS)-8-bromo-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile; compound with (3S,4aS,12bR)-8-bromo-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazole-12b-carbonitrile (105, R1=4-Fluorophenyl, R3=Trifluoromethyl) (1.35 g, 68% yield) as an ivory solid. LC/MS, method 3, Rt=2.36 min, MS m/z 524 and 526 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.36 (s, 1H), 8.09 (s, 1H), 7.62-7.53 (m, 2H), 7.42-7.32 (m, 2H), 6.30 (s, 1H), 4.54-4.43 (m, 1H), 3.59-3.47 (m, 1H), 2.57-2.40 (m, 2H), 2.41-2.29 (m, 1H), 2.25-2.03 (m, 2H), 2.01-1.83 (m, 3H), 1.63-1.51 (m, 1H).

Workup

  1. additionwas added dropwise over about 5 min
  2. waitAfter about 2 h
  3. waitAfter about 2 h
  4. customthe volatiles were removed under reduced pressure
  5. dissolutionThe residue was dissolved in THF (40.0 mL)
  6. waitAfter about 1 h
  7. customThe layers were separated
  8. washthe organic layer was washed with aq. NaCl (50 mL)
  9. dry with materialthen dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. additionDCM (5 mL) was added
  13. filtrationthe solid was collected by filtration
  14. washrinsing with DCM (2×2 mL)
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-7abd809c00b04d47a6a2daebf566194c
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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