1,3-Dichloroacetone → Tert-butyl 4-[4-(chloromethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate

HRID 1408321Notes

Reaction equation

HRID 1408321 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[S:16])[NH2:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][CH2:18][C:19]([CH2:21]Cl)=O.[O-]S([O-])(=O)=O.[Mg+2]>CC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:16][CH:21]=[C:19]([CH2:18][Cl:17])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 107931,3-DichloroacetoneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 2735648tert-Butyl 4-carbamothioylpiperidine-1-carboxylate

Product 1

HCID 57423790Tert-butyl 4-[4-(chloromethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 4-thiocarbamoyl-piperidine-1-carboxylic acid tert-butyl ester (4.9 g, 20 mmol) in acetone (80 mL) was added 1,3-dichloroacetone (3.3 g, 26 mmol), MgSO4 (3.6 g, 30 mmol) and MgCO3 (1.68 g, 20 mmol). The mixture was heated under reflux overnight, cooled and filtered through celite. The solvent was removed in vacuo and the residue was redissolved with EtOAc (150 mL). The resulting solution was washed successively with 5% NaHSO3, saturated NaHCO3, and brine. After drying (Na2SO4), the solvent was removed to afford the desired product. 1H NMR (CDCl3): δ 7.20 (1H, s), 4.67 (2H, s), 4.20 (2H, br), 3.16 (1H, m), 2.87 (2H, m), 2.09 (2H, m), 1.72 (2H, m), 1.47 (9H, s).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux overnight
  3. temperaturecooled
  4. filtrationfiltered through celite
  5. customThe solvent was removed in vacuo
  6. dissolutionthe residue was redissolved with EtOAc (150 mL)
  7. washThe resulting solution was washed successively with 5% NaHSO3, saturated NaHCO3, and brine
  8. dry with materialAfter drying (Na2SO4)
  9. customthe solvent was removed

Sources & evidence

ORD record
ord-cefa01d8579544d894ee56eee3fe613f
Source dataset
uspto-grants-2014_12
Patent number
US08921350B2

Reaction notes

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