Cesium carbonate → Tert-butyl 4-(1-{[6-(trifluoromethyl)pyridin-2-yl]thio}ethyl)piperidine-1-carboxylate

HRID 1873848Notes

Reaction equation

HRID 1873848 reaction equation
[SH:1][CH:2]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)[CH3:3].Br[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[N:19]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1>[F:25][C:24]([F:27])([F:26])[C:20]1[N:19]=[C:18]([S:1][CH:2]([CH:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:8][CH2:9]2)[CH3:3])[CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27829022-Bromo-6-(trifluoromethyl)pyridineHCID 59447341tert-Butyl 4-(1-mercaptoethyl)piperidine-1-carboxylate

Product 1

HCID 59447422Tert-butyl 4-(1-{[6-(trifluoromethyl)pyridin-2-yl]thio}ethyl)piperidine-1-carboxylateYield 94.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a 16 ml vial was added tert-butyl 4-(1-mercaptoethyl)piperidine-1-carboxylate (500 mg, 2.04 mmol), 2-bromo-6-(trifluoromethyl)pyridine (460 mg, 2.04 mmol), Pd(dppf)Cl2 (42 mg, 0.051 mmol) and Cs2CO3 (996 mg, 3.06 mmol) and 4 ml toluene. The vial was flushed with nitrogen, sealed and heated at 75° C. for 36 hours. After cooling to room temperature, the reaction mixture was diluted with 30 ml ether, and washed with 30 ml water. The organics were dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel column eluted with 1:9 to 1:4 ethyl acetate/hexane to give 750 mg desired product was light yellow oil.

Workup

  1. customThe vial was flushed with nitrogen
  2. customsealed
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction mixture was diluted with 30 ml ether
  5. washwashed with 30 ml water
  6. dry with materialThe organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on silica gel column
  10. washeluted with 1:9 to 1:4 ethyl acetate/hexane

Sources & evidence

ORD record
ord-6959e05b06894ce2ae505021ec0458a0
Source dataset
uspto-grants-2012_11
Patent number
US08304434B2

Reaction notes

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