Trifluoroacetic acid → HCID 51049976, compound

HRID 2092964Notes

Reaction equation

HRID 2092964 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[C:13]1([C:19]#[C:20][C:21]2[S:22][C:23]([C:26]([OH:28])=O)=[CH:24][N:25]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[NH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.FC(F)(F)C(O)=O>O1CCCC1.CCOC(C)=O>[C:13]1([C:19]#[C:20][C:21]2[S:22][C:23]([C:26]([N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[O:28])=[CH:24][N:25]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 682631,1'-CarbonyldiimidazoleHCID 58227488HCID 58227488, compound2×

Product 1

HCID 51049976HCID 51049976, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N,N-Carbonyldiimidazole (790 mg, 4.87 mmol) (Fluka Chemie AG) was added to a solution of 2-phenylethynyl-thiazole-5-carboxylic acid (1.00 g, 4.36 mmol) [Intermediate 1] in tetrahydrofuran (17.4 mL) and stirred for 60 minutes. Piperidine (3.03 g, 35.6 mmol) and trifluoroacetic acid (295 μL, 3.83 mmol) were added and the mixture was stirred for 20 hours. The yellow solution was diluted with 150 mL of EtOAc and washed with 3.7 M HCl solution (5×30 mL), water (1×30 mL), 1.0 M K2CO3 (4×30 mL), water (2×30 mL), brine (1×30 mL), dried (Na2SO4) and concentrated to give a light tan solid (94% pure by LC/MS). The sample was further purified by silica gel chromatography over a 40 g SiO2 column using a gradient elution from 25% EtOAc in hexanes to 30% EtOAc in hexanes over 30 minutes to give title compound (2-phenylethynyl-thiazol-5-yl)-piperidin-1-yl-methanone (797 mg, 62%) as a light yellow powder. 1H NMR (300 MHz, CDCl3) δ 7.94 (s, 1H), 7.63-7.59 (m, 2H), 7.46-7.36 (m, 3H), 3.69-3.67 (m, 4H), 1.78-1.62 (m, 6H). LCMS (Method 1), RT=1.41. Calculated [M+H]+=297; Observed [M+H]+=297.

Workup

  1. stirringthe mixture was stirred for 20 hours
  2. washwashed with 3.7 M HCl solution (5×30 mL), water (1×30 mL), 1.0 M K2CO3 (4×30 mL), water (2×30 mL), brine (1×30 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customto give a light tan solid (94% pure by LC/MS)
  6. customThe sample was further purified by silica gel chromatography over a 40 g SiO2 column
  7. washa gradient elution from 25% EtOAc in hexanes to 30% EtOAc in hexanes over 30 minutes

Sources & evidence

ORD record
ord-c2040f73edcd470097fc602b7e4a13eb
Source dataset
uspto-grants-2013_05
Patent number
US08440837B2

Reaction notes

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