Toluene → 2-(4-Chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one

HRID 554836Notes

Reaction equation

HRID 554836 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:16]([OH:18])=[O:17])=[C:11]([CH2:13][CH2:14]O)[N:12]=2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]3[C:16](=[O:17])[O:18][CH2:14][CH2:13][C:11]=3[N:12]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 1140TolueneHCID 575016942-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid

Product 1

HCID 574214852-(4-Chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-oneYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Mix 2-(4-chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid (81.2 g, 286.2 mmol) with p-TsOH monohydrate (32.0 g, 168.2 mmol) and toluene (1200 mL). Heat the slurry to reflux during which time the solids dissolve. Stir the resulting tan solution mechanically for 2 h, using a Dean-Stark trap to collect water (21 mL). Cool the solution to room temperature and add saturated aqueous NaHCO3 (1700 mL) and EtOAc (1700 mL). Separate the organic solution, then extract the aqueous layer with EtOAc (2×1700 mL). Combine the organic solutions, wash with brine (1700 mL), and concentrate in vacuo to give a solid. Mix the solid with CH2Cl2 (500 mL) and concentrate in vacuo and repeat two times to give 60.1 g (79%) of the title compound. ES/MS m/z (35Cl) 266.0 [M+1]+.

Workup

  1. temperatureHeat the slurry
  2. temperatureto reflux during which time the solids
  3. dissolutiondissolve
  4. customto collect water (21 mL)
  5. additionadd saturated aqueous NaHCO3 (1700 mL) and EtOAc (1700 mL)
  6. customSeparate the organic solution
  7. extractionextract the aqueous layer with EtOAc (2×1700 mL)
  8. washCombine the organic solutions, wash with brine (1700 mL)
  9. concentrationconcentrate in vacuo
  10. customto give a solid
  11. concentrationconcentrate in vacuo and repeat two times

Sources & evidence

ORD record
ord-13b653c67742464398ed86d51009baec
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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