Methyl iodide → Tert-butyl 4-(1-methyl-1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate

HRID 1873831Notes

Reaction equation

HRID 1873831 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([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:7][CH:8]=1.[CH3:29][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI.[NH4+].[Cl-]>CCOCC.O.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:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:27])[F:28])[CH:4]=1)(=[O:10])=[O:11])[CH3:29]

Participants

8

Reactant 4

HCID 6328Methyl iodide2×HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 59447342Tert-butyl 4-(1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate

Product 1

HCID 59447405Tert-butyl 4-(1-methyl-1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a 100 ml round bottom flask was added tert-butyl 4-(1-{[3-(trifluoromethyl)phenyl]sulfonyl}ethyl)piperidine-1-carboxylate (5.4 g, 12.8 mmol) and 30 ml tetrahydrofuran. The resulting solution was cooled to −78° C. Sodium bis(trimethylsilyl)amide (NaHMDS) tetrahydrofuran solution (1M, 15.4 ml) was added via a syringe. The reaction mixture turned deep orange-red. It was stirred at −78 C for 5 minutes. MeI (0.96 ml, 15.4 mmol) was then added dropwise with a syringe until reaction mixture turned light yellow. More NaHMDS (1M, 3 ml tetrahydrofuran solution) was added. The reaction mixture was stirred at −78° C. for 5 more minutes and 0.3 ml MeI was added. NH4Cl (60 ml) was added at −78° C. to quench the reaction. The resulting mixture was diluted with 120 ml ether and 60 ml water. 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 ethylacetate/hexane to give desired product which was used for the next directly.

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. customThe layers were separated
  5. dry with materialthe organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel column
  9. washeluted with 1:4 to 1:2 ethylacetate/hexane

Sources & evidence

ORD record
ord-be1c198625174d4191caac250a417b64
Source dataset
uspto-grants-2012_11
Patent number
US08304434B2

Reaction notes

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