Piperidine-1-carbothioamide → 4-(4-Fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(1-piperidinyl)-thiazole

HRID 1378589Notes

Reaction equation

HRID 1378589 reaction equation
Br[CH:2]([C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=O.[N:22]1([C:28](=[S:30])[NH2:29])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>C(O)C.C(Cl)Cl>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:29]=[C:28]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[S:30][C:2]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 1551232Piperidine-1-carbothioamideHCID 112340792-Bromo-1-(4-fluorophenyl)-2-(4-(methylsulfonyl)phenyl)ethanone

Product 1

HCID 229117134-(4-Fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(1-piperidinyl)-thiazoleYield 72%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (0.462 g, 1.24 mmol) (Example 26, Step 2) in ethanol (10 mL) in a 25 mL round bottom flask was added piperidine thiocarboxamide (0.198 g, 1.37 mmol) and the solution was heated to reflux for 14 hours. The reaction was cooled to room temperature and concentrated in vacuo yielding a foam. This foam was dissolved in methylene chloride and washed successively with NaHCO3 saturated solution (3 portions) and brine, dried over Na2SO4, filtered and reconcentrated in vacuo yielding 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(1-piperidinyl)-thiazole (0.371 g, 72%) as a yellow-green fluffy solid: mp 173°-175° C., 1H NMR (CDCl3) 400 mHz δ7.77 (d, J=8.56 Hz, 2H), 7.46 (dd, J=5.60, 8.80), 7.38 (d, J=8.56 Hz, 2H), 6.99 (t, J=8.80 Hz, 2H), 3.53 (s (broad), 4H), 3.05 (s, 3H), 1.70 (s (broad), 6H). MS (EI): m/z 417 (MH+). HRMS Δ=-1.5 mmu.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 14 hours
  3. concentrationconcentrated in vacuo
  4. customyielding a foam
  5. washwashed successively with NaHCO3 saturated solution (3 portions) and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered

Sources & evidence

ORD record
ord-738272fce64d454a90d3e308146a8dbc
Source dataset
uspto-grants-1997_09
Patent number
US05668161

Reaction notes

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