Methyl iodide → Tert-butyl 4-(1-methyl-1-{[6-(trifluoromethyl)pyridin-2-yl]sulfonyl}ethyl)piperidine-1-carboxylate

HRID 1873849Notes

Reaction equation

HRID 1873849 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[N:8]=[C:7]([S:9]([CH:12]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH3:13])(=[O:11])=[O:10])[CH:6]=[CH:5][CH:4]=1.[CH3:29][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI>O1CCCC1>[CH3:13][C:12]([CH:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:18][CH2:19]1)([S:9]([C:7]1[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:27])[F:28])[N:8]=1)(=[O:10])=[O:11])[CH3:29]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59447406Tert-butyl 4-(1-{[6-(trifluoromethyl)pyridin-2-yl]sulfonyl}ethyl)piperidine-1-carboxylate

Product 1

HCID 59447129Tert-butyl 4-(1-methyl-1-{[6-(trifluoromethyl)pyridin-2-yl]sulfonyl}ethyl)piperidine-1-carboxylateYield 99.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a 50 ml round bottom flask was added tert-butyl 4-(1-{[6-(trifluoromethyl)pyridin-2-yl]sulfonyl}ethyl)piperidine-1-carboxylate (0.78 g, 1.85 mmol) and tetrahydrofuran (10 ml). The resulting solution was cooled with dry ice acetone bath. Sodium bis(trimethylsilyl)amide (NaHMDS) tetrahydrofuran solution (1M, 2.58 ml, 2.58 mmol) was added via a syringe. The resulting reaction solution was stirred at −78° C. for 10 minutes. MeI (0.173 ml, 2.77 mmol) was added. The reaction mixture was allowed to warm up to room temperature and quenched by addition of 50 ml saturated NH4Cl solution. It was diluted with 30 ml ether. The layers were separated, and the organics were dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel column eluted with 1:4 to 1:2 ethyl acetate/hexane to give 0.806 g desired product (contains solvent).

Workup

  1. temperatureThe resulting solution was cooled with dry ice acetone bath
  2. customThe resulting reaction solution
  3. temperatureto warm up to room temperature
  4. customquenched by addition of 50 ml saturated NH4Cl solution
  5. additionIt was diluted with 30 ml ether
  6. customThe layers were separated
  7. dry with materialthe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified on silica gel column
  11. washeluted with 1:4 to 1:2 ethyl acetate/hexane

Sources & evidence

ORD record
ord-d90577bc9cf24339962cf6cc5a5e7dde
Source dataset
uspto-grants-2012_11
Patent number
US08304434B2

Reaction notes

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