Water → HCID 58169868, compound

HRID 472692Notes

Reaction equation

HRID 472692 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:35])[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([N+:24]([O-:26])=[O:25])[CH2:20][C@@H:19]2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[CH3:34])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F-].[K+].[C:40]([O:48][CH3:49])(=[O:47])/[CH:41]=[CH:42]\[C:43]([O:45][CH3:46])=[O:44].O>CS(C)=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([N:15]([CH3:35])[C:16]([N:18]2[CH2:23][CH2:22][C@@:21]([CH:42]([CH2:41][C:40]([O:48][CH3:49])=[O:47])[C:43]([O:45][CH3:46])=[O:44])([N+:24]([O-:26])=[O:25])[CH2:20][C@@H:19]2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[CH3:34])=[O:17])[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:36])[F:37])[CH:8]=1

Participants

8

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 5271565Dimethyl maleateHCID 58169882HCID 58169882, compound2×

Product 1

HCID 58169868HCID 58169868, compoundYield 61.1%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Procedure

(2R)-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-nitro-1-piperidinecarboxamide (Intermediate 38, 500 mg, 0.934 mmol) was dissolved in Dimethyl Sulfoxide (DMSO) (6 ml) and to this solution were added potassium fluoride (271 mg, 4.67 mmol) and tetrabutylammonium iodide (345 mg, 0.934 mmol). The mixture was left stirring at rt for 10 min (pink mixture), then dimethyl maleate (0.584 ml, 4.67 mmol) was added. The mixture was left stirring at rt for 4 hrs and at 40° C. for 1 hr, then water and Et2O were added. The two phases were separated and the organic one was washed with 1N HCl. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude was purified by flash chromatography (40M cartridge; eluting from 9:1 to 7:3 Cy:EtOAc) to give two batches of the title compound:

Workup

  1. waitThe mixture was left
  2. waitThe mixture was left
  3. stirringstirring at rt for 4 hrs and at 40° C. for 1 hr
  4. customThe two phases were separated
  5. washthe organic one was washed with 1N HCl
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customThe crude was purified by flash chromatography (40M cartridge; eluting from 9:1 to 7:3 Cy:EtOAc)

Sources & evidence

ORD record
ord-f09cd2a8ef544419b13f77626e5f63e8
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

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