Sodium Iodide → (+/-)-Methyl(cis)-1-[2,5-bis(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate

HRID 1869744

Reaction equation

HRID 1869744 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:14][C@@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[F:21][C:22]([F:36])([F:35])[C:23]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:24]=1[CH2:25]Br.[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[F:21][C:22]([F:35])([F:36])[C:23]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:27][C:24]=1[CH2:25][N:10]1[CH2:11][CH2:12][C@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:14][C@@H:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:19])([F:1])[F:20])=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 27731992-(Bromomethyl)-1,4-bis(trifluoromethyl)benzeneHCID 86617995Methyl(cis)-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate

Product 1

HCID 86617996(+/-)-Methyl(cis)-1-[2,5-bis(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylateYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

(±)-Methyl(cis)-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate (Example (18b) (88 mg), 2,5-bis(trifluoromethyl)benzyl bromide (110 mg), NaI (25 mg) and K2CO3 (100 mg) in DMF (3 ml) were placed in a microwave tube and the contents were heated in the microwave oven for 20 min at 150° C. The cooled mixture was dispersed between water and EtOAc and the organic extracts were washed with sodium thiosulfate, brine, dried (MgSO4) and evaporated. The crude oil was purified by chromatography on silica using 5-8% EtOAc in hexane to yield a colourless oil (98 mg, 62%) which crystallized on standing. 1H NMR (400 MHz, CDCl3) δ: 1.81-1.89 (2H, m), 1.97 (1H, d, J 13.2), 2.09-2.17 (2H, m), 2.49-2.56 (1H, m), 2.94-2.96 (1H, m), 3.34 (1H, d, J 15.6), 3.40 (1H, dd, J 2.6, 11.3), 3.66 (4H, d, J 15.6), 7.53-7.59 (5H, m), 7.68 (1H, d, J 8.2), 8.19 (1H, s); M/Z (ES+) 514 (MH+).

Workup

  1. washthe organic extracts were washed with sodium thiosulfate, brine
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customThe crude oil was purified by chromatography on silica using 5-8% EtOAc in hexane

Sources & evidence

ORD record
ord-864491509d5a4c3287fbef81997926f5
Source dataset
uspto-grants-2009_12
Patent number
US07638629B2

Linked notes

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