Triethylamine → 2-(4-(Trifluoromethyl)piperidin-1-ylsulfonyl)benzonitrile

HRID 272787Notes

Reaction equation

HRID 272787 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9](Cl)(=[O:11])=[O:10])#[N:2].C(N(CC)CC)C.Cl.[F:21][C:22]([F:30])([F:29])[CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C1COCC1>[F:21][C:22]([F:30])([F:29])[CH:23]1[CH2:28][CH2:27][N:26]([S:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:1]#[N:2])(=[O:11])=[O:10])[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5223472-Cyanobenzenesulfonyl ChlorideHCID 162181604-(Trifluoromethyl)piperidine hydrochloride

Product 1

HCID 655362792-(4-(Trifluoromethyl)piperidin-1-ylsulfonyl)benzonitrileYield 29.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 2-cyanobenzene-1-sulfonyl chloride (201 mg, 1.00 mmol) in THF (5 mL), triethylamine (0.84 mL, 6.00 mmol) and 4-trifluoromethylpiperidine hydrochloride (284 mg, 1.50 mmol) were added. After stirring for 2 h, the reaction was concentrated and diluted with ethyl acetate and washed with water. After drying (Na2SO4), filtering, and concentrating, the residue was purified via silica gel chromatography eluting with 45% ethyl acetate/hexanes to provide 2-(4-(trifluoromethyl)piperidin-1-ylsulfonyl)benzonitrile [95 mg, LC-MS: 319.19 (M+H)+]. The product (52 mg) was dissolved in MeOH (5 mL), conc. HCl (25.0 mg) was added, and the whole was hydrogenated at 50 psi overnight. The reaction was concentrated and purified via preparative HPLC(CH3CN/water/TFA) to provide 210A. LC-MS: 323.21 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. dry with materialAfter drying (Na2SO4)
  5. filtrationfiltering
  6. concentrationconcentrating
  7. customthe residue was purified via silica gel chromatography
  8. washeluting with 45% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b21f93717403474492727c08123cbf6d
Source dataset
uspto-grants-2008_11
Patent number
US07456195B2

Reaction notes

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