(Trifluoromethyl)trimethylsilane → HCID 131736646, compound

HRID 1481626Notes

Reaction equation

HRID 1481626 reaction equation
[C:1]([C@H:4]1[O:12][C@H:11]2[C@H:7]([N:8]=[C:9]([N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[S:10]2)[C@H:6]([F:22])[C@@H:5]1[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:3])[CH3:2].[Si]([C:35]([F:38])([F:37])[F:36])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.[Cl-].[Na+].O>[CH2:24]([O:23][C@@H:5]1[C@@H:4]([C@:1]([OH:3])([CH3:2])[C:35]([F:38])([F:37])[F:36])[O:12][C@H:11]2[C@H:7]([N:8]=[C:9]([N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[S:10]2)[C@@H:6]1[F:22])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2×HCID 123961783HCID 123961783, compound

Product 1

HCID 131736646HCID 131736646, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of tert-butyl ((3aR,5S,6R,7S,7aR)-5-acetyl-6-(benzyloxy)-7-fluoro-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.310 g, 0.704 mmol) and TMSCF3 (0.299 g, 2.10 mmol) in anhydrous THF (12 mL) was added TBAF (1.0 M in THF, 0.040 mL, 0.040 mmol). After addition the reaction mixture was stirred at room temperature for 16 h. Another batch of TBAF (1.0 M in THF, 1.2 mL, 1.2 mmol) was added at 0° C., and the mixture was stirred at room temperature for another 2 h. The reaction solution was then diluted with brine (50 mL), and extracted with EtOAc (2×30 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 1:2), affording tert-butyl ((3aR,5S,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-((R)-1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.178 g, 50%) as a white foam, 1H NMR (major isomer) (400 MHz, CDCl3) δ 7.37-7.28 (m, 5H), 6.18 (d, J=7.7 Hz, 1H), 5.08 (td, J=4.3, 45.6 Hz, 1H), 4.92 (d, J=10.7 Hz, 1H), 4.67-4.60 (m, 1H), 4.49 (d, J=10.7 Hz, 1H), 4.27-4.22 (m, 1H), 3.66-3.92 (m, 1H), 3.28 (s, 3H), 3.05 (s, br. 1H), 1.54 (s, 9H), 1.38 (s, 3H); and tert-butyl ((3aR,5S,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-((S)-1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.136 g, 38%) as a white foam, 1H NMR (minor isomer) (400 MHz, CDCl3) δ 7.37-7.28 (m, 5H), 6.19 (d, J=7.7 Hz, 1H), 5.05 (td, J=4.3, 45.7 Hz, 1H), 4.94 (d, J=10.7 Hz, 1H), 4.64-4.60 (m, 1H), 4.49 (d, J=10.7 Hz, 1H), 4.26-4.24 (m, 1H), 3.90 (d, J=7.5 Hz, 1H), 3.29 (s, 3H), 3.25 (s, br. 1H), 1.54 (s, 9H), 1.37 (s, 3H). The stereochemistry for each isomer was assigned randomly.

Workup

  1. additionAfter addition the reaction mixture
  2. stirringthe mixture was stirred at room temperature for another 2 h
  3. extractionextracted with EtOAc (2×30 mL)
  4. extractionThe combined extract
  5. dry with materialwas dried over anhydrous Na2SO4
  6. filtrationAfter filtration the solvent
  7. customwas evaporated under reduced pressure
  8. customthe residue was purified
  9. customseparated on silica gel by automatic flash column chromatography (EtOAc/hexanes, 1:10 to 1:2)

Sources & evidence

ORD record
ord-ceb5d993b87640d0a6003855d77cb321
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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