Piperidine-1-carbothioamide → 4-[2-(Dimethylamino)-1,3-thiazol-4-yl]benzoic acid

HRID 606599Notes

Reaction equation

HRID 606599 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=1)=O.[N:14]1([C:20](=[S:22])[NH2:21])[CH2:19]CCC[CH2:15]1>C1COCC1>[CH3:15][N:14]([CH3:19])[C:20]1[S:22][CH:2]=[C:3]([C:5]2[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=2)[N:21]=1

Participants

4

Reactant 2

HCID 1551232Piperidine-1-carbothioamideHCID 27568364-(2-bromoacetyl)benzoic Acid

Product 1

HCID 582568424-[2-(Dimethylamino)-1,3-thiazol-4-yl]benzoic acidYield 32.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of thiocarbonyldiimidazole (44.9 mmol) in THF (40 mL) at room temperature was added portionwise 2 M Dimethylamine in THF (44 mmol) and a temperature increase was observed. 40 min after final addition the reaction mixture was heated to 55° C. for 1 h, then allowed to reach room temperature again. The reaction was then concentrated in vacuo and the residue purified by flash chromatography (silica gel, Petroleum ether-EtOAc) to give the intermediate imidazole-1-carbothioic acid dimethylamide. This material was treated with freshly prepared sat. ammonia in methanol (40 ml) for 60 h, then concentrated in vacuo and the precipitated residue was suspended in diethyl ether and collected by filtration. The precipitate was washed with diethyl ether and air-dried to give a slight yellow solid (1.71 g, 16.4 mmol) which was used in the subsequent step. 4-(2-bromoacetyl)benzoic acid (1.23 mmol) and 1-piperidinethiocarboxamide (1.23 mmol) were mixed in THF (10 mL), then refluxed for 3 h. The reaction mixture was then allowed to reach room temperature and the obtained precipitate was collected by filtration and washed with 3 portions of diethyl ether. The crude product was crystallized from hot 1:1 EtOH-EtOAc to give a first harvest of colorless needles (0.1 g, 0.40 mmol). 1H NMR (DMSO-d6, 400 MHz) δ 7.94 (4H, m), 7.37 (1H, s), 3.11 (6H, m).

Workup

  1. temperaturerefluxed for 3 h
  2. customto reach room temperature
  3. filtrationthe obtained precipitate was collected by filtration
  4. washwashed with 3 portions of diethyl ether
  5. customThe crude product was crystallized from hot 1:1 EtOH-EtOAc

Sources & evidence

ORD record
ord-821dd6b61e8a4e12b0619e033a36591a
Source dataset
uspto-grants-2011_03
Patent number
US07915300B2

Reaction notes

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