(Trifluoromethyl)trimethylsilane → HCID 123531119, compound

HRID 1481624Notes

Reaction equation

HRID 1481624 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:17]([CH:18]=[O:19])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[S:14]2)[C@@H:10]1[F:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si]([C:34]([F:37])([F:36])[F:35])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O.[Cl-].[Na+].O>[CH2:1]([O:8][C@@H:9]1[C@@H:17]([C@H:18]([OH:19])[C:34]([F:37])([F:36])[F:35])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[S:14]2)[C@@H:10]1[F:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2×HCID 123295653HCID 123295653, compound

Product 1

HCID 123531119HCID 123531119, compoundYield 34.4%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of tert-butyl ((3aR,5S,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-formyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.352 g, 0.829 mmol) and TMSCF3 (0.290 g, 2.04 mmol) in anhydrous THF (15 mL) was added TBAF (1.0 M in THF, 0.050 mL, 0.050 mmol). After addition the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was cooled at 0° C., and another batch of TBAF (1.0 M in THF, 1.5 mL, 1.5 mmol) was added. The mixture was stirred at room temperature for another 2 h, and then diluted with EtOAc (20 mL) and brine (50 mL). The organic layer was collected, and the aqueous was extracted with EtOAc (20 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified and separated on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:10 to 2:3), affording tert-butyl ((3aR,5R,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-((S)-2,2,2-trifluoro-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate as a pale yellow solid (0.141 g, 34%). 1H NMR (400 MHz, CDCl3) δ 7.37-7.28 (m, 5H), 6.14 (d, J=7.5 Hz, 1H), 5.09 (td, J=4.1, 46.4 Hz, 1H), 4.87 (d, J=10.8 Hz, 1H), 4.38-4.30 (m, 1H), 4.50 (d, J=10.8 Hz, 1H), 4.25-4.22 (m, 1H), 4.10-4.06 (m, 2H), 3.27 (s, 3H), 1.52 (s, 9H).

Workup

  1. additionAfter addition the reaction mixture
  2. temperatureThe reaction mixture was cooled at 0° C.
  3. stirringThe mixture was stirred at room temperature for another 2 h
  4. customThe organic layer was collected
  5. extractionthe aqueous was extracted with EtOAc (20 mL)
  6. extractionThe combined extract
  7. dry with materialwas dried over anhydrous Na2SO4
  8. filtrationAfter filtration the solvent
  9. customwas evaporated under reduced pressure
  10. customthe residue was purified
  11. customseparated on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:10 to 2:3)

Sources & evidence

ORD record
ord-b99fa18c2c454845a499a73ae2f0d5c0
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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