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

HRID 2276939Notes

Reaction equation

HRID 2276939 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-trifluoromethylpyridine (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-7e1e57e1bb12405781ae2378a17e36e0
Source dataset
uspto-grants-2015_09
Patent number
US09133145B2

Reaction notes

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