(Trifluoromethyl)trimethylsilane → HCID 59722702, compound

HRID 1664855Notes

Reaction equation

HRID 1664855 reaction equation
[F:1][C:2]([Si](C)(C)C)([F:4])[F:3].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:27]([C:30]1[N:34]2[CH2:35][C@H:36]([C:48]3[CH:53]=[CH:52][CH:51]=[C:50]([F:54])[C:49]=3[F:55])[CH2:37][CH2:38][C@@H:39]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:33]2=[N:32][CH:31]=1)(=[O:29])[CH3:28]>O1CCCC1>[F:55][C:49]1[C:50]([F:54])=[CH:51][CH:52]=[CH:53][C:48]=1[C@H:36]1[CH2:35][N:34]2[C:30]([C:27]([OH:29])([CH3:28])[C:2]([F:4])([F:3])[F:1])=[CH:31][N:32]=[C:33]2[C@H:39]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:38][CH2:37]1

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilane2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 59722739HCID 59722739, compound

Product 1

HCID 59722702HCID 59722702, compoundYield 31.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(Trifluoromethyl)trimethylsilane (0.273 mL, 1.85 mmol) and tetrabutylammonium fluoride (1.0 M in tetrahydrofuran; 74 μL, 0.074 mmol) were sequentially added to a solution of tert-butyl (6S,9R)-3-acetyl-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-ylcarbamate (150 mg, 0.37 mmol) in tetrahydrofuran (1 mL). After 5 min, additional (trifluoromethyl)trimethylsilane (100 μL, 0.678 mmol) and tetrabutylammonium fluoride (1.0 M in tetrahydrofuran; 25 μL, 0.025 mmol) were added. After 30 min, the reaction mixture was quenched with saturated sodium bicarbonate. The mixture was extracted with dichloromethane (3×), and the combined organic extracts were washed with water, saturated brine, dried over sodium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (55 mg). MS 476.2 (M+1).

Workup

  1. waitAfter 30 min
  2. customthe reaction mixture was quenched with saturated sodium bicarbonate
  3. extractionThe mixture was extracted with dichloromethane (3×)
  4. washthe combined organic extracts were washed with water, saturated brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-9d59b8fc78be47969afc4c6b53f35882
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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