Trifluoroacetic anhydride → 2-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzonitrile

HRID 1269526Notes

Reaction equation

HRID 1269526 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([C:19]3[S:23][C:22]([C:24]4[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=4)=[N:21][C:20]=3[CH3:34])=[O:18])[CH2:12]2)=[CH:7][C:3]=1[C:4]([NH2:6])=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1.C(OCC)C>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([C:19]3[S:23][C:22]([C:24]4[CH:25]=[CH:26][C:27]([C:30]([F:33])([F:31])[F:32])=[CH:28][CH:29]=4)=[N:21][C:20]=3[CH3:34])=[O:18])[CH2:12]2)=[CH:7][C:3]=1[C:4]#[N:6]

Participants

5

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 10254897(R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide

Product 1

HCID 184484662-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzonitrileYield 118.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

(R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide (230 mg, 0.47 mmol) was dissolved in pyridine (5 mL) and cooled to 0° C. Trifluoroacetic anhydride (0.67 mL, 4.72 mmol) was added dropwise. Stirred for 1 h at 0° C. after addition. The reaction was diluted with diethyl ether (100 mL) and washed with 1 N HCl (2×100 mL) and saturated NaHCO3 (100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 33% ethyl acetate/hexanes to yield 262 mg (97%) of the desired 2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzonitrile as a clear oil.

Workup

  1. additionafter addition
  2. washwashed with 1 N HCl (2×100 mL) and saturated NaHCO3 (100 mL)
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customchromatographed with 33% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-46063991701a442da3857f1e258ee78f
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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