Thiophenol → Methyl 1-[4-(5-trifluoromethylpyridin-2-yl)-piperazin-1-yl]-cyclopropanecarboxylate

HRID 1361432Notes

Reaction equation

HRID 1361432 reaction equation
[N+](C1C=CC=CC=1S([N:13]1[CH2:18][CH2:17][N:16]([C:19]2([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20]2)[CH2:15][CH2:14]1)(=O)=O)([O-])=O.C(=O)([O-])[O-].[K+].[K+].C1(S)C=CC=CC=1.Br[C:40]1[CH:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][N:41]=1>CN(C)C=O.C(OCC)(=O)C>[F:47][C:46]([F:49])([F:48])[C:43]1[CH:44]=[CH:45][C:40]([N:13]2[CH2:14][CH2:15][N:16]([C:19]3([C:22]([O:24][CH3:25])=[O:23])[CH2:20][CH2:21]3)[CH2:17][CH2:18]2)=[N:41][CH:42]=1

Participants

7

Reactant 4

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 66628127Methyl 1-[4-(2-nitrobenzenesulfonyl)-piperazin-1-yl]-cyclopropanecarboxylate

Product 1

HCID 66628341Methyl 1-[4-(5-trifluoromethylpyridin-2-yl)-piperazin-1-yl]-cyclopropanecarboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 1-[4-(2-nitrobenzenesulfonyl)-piperazin-1-yl]-cyclopropanecarboxylate (0.60 g, 1.63 mmol) from Example 16C in anhydrous dimethylformamide (5 mL) was treated with potassium carbonate (0.67 g, 4.88 mmol) and thiophenol (0.21 g, 1.95 mmol) and stirred one hour at room temperature. This reaction mixture was then treated with 2-bromo-5-trifluoromethyl pyridine (0.44 g, 1.95 mmol) and heated overnight at 80° C. Reaction diluted with ethyl acetate, washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by normal phase HPLC on a Biotage pre-packed silica gel column eluting with 9:1 hexane:ethyl acetate to afford the title compound. MS(ESI) m/z 330 (M+H)+.

Workup

  1. temperatureheated overnight at 80° C
  2. customReaction
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by normal phase HPLC on a Biotage pre-packed silica gel column
  8. washeluting with 9:1 hexane

Sources & evidence

ORD record
ord-4906c7dcb0734b10afcef6408bcc9539
Source dataset
uspto-grants-2011_02
Patent number
US07880001B2

Reaction notes

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