4-Toluenesulfonyl chloride → methyl 1,1-dimethyl-3-(pyrid-3-yl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylate

HRID 2210596Notes

Reaction equation

HRID 2210596 reaction equation
C1(C)C=CC(S(Cl)(=O)=O)=CC=1.Cl[CH:13]([CH2:18]Cl)[C:14]([O:16][CH3:17])=[O:15].[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]2[N:30]([CH:31]=O)[CH:29](C(O)=O)[C:28]([CH3:37])([CH3:36])[S:27]2)[CH:21]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:36][C:28]1([CH3:37])[S:27][CH:26]([C:22]2[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=2)[N:30]2[CH:31]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:29]12

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471Triethylamine2×HCID 95429Propanoic acid, 2,3-dichloro-, methyl esterHCID 133392752-(3-Pyridinyl)-3-formyl-5,5-dimethyl-4-thiazolidinecarboxylic acid

Product 1

HCID 19379134methyl 1,1-dimethyl-3-(pyrid-3-yl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylateYield 20.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of p-toluenesulfonyl chloride (18 g, 95 mmol) and methyl 2,3-dichloropropionate (15 g, 95 mmol) in refluxing CH2Cl2 (125 mL) was added a mixture of 2-(3-pyridinyl)-3-formyl-5,5-dimethyl-4-thiazolidinecarboxylic acid (5.1 g, 19 mmol) and triethylamine (2.3 g, 22 mmol) in CH2Cl2 (125 mL). After one hour at reflux triethylamine (4.6 g, 44 mmol) was added and the reaction mixture was refluxed for a further 17 hours. The reaction mixture was cooled to ambient temperature and partitioned between cold 1N aqueous NaOH and ethyl acetate. The organic phase was washed with cold 1N aqueous NaOH and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was dissolved in 5% aqueous HCl and the solution was extracted twice with ether. The aqueous phase was neutralized with solid Na2CO3 and extracted twice with ethyl acetate. The combined ethyl acetate extracts where washed with brine, dried over MgSO4, and concentrated in vacuo. Chromatography on silica gel (150 g, 1:1 ethyl acetate, hexanes), afforded methyl 1,1-dimethyl-3-(pyrid-3-yl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylate (1.1 g, 20%) as an off-while powder.

Workup

  1. additionwas added
  2. additionwas added
  3. temperaturethe reaction mixture was refluxed for a further 17 hours
  4. custompartitioned between cold 1N aqueous NaOH and ethyl acetate
  5. washThe organic phase was washed with cold 1N aqueous NaOH and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude product was dissolved in 5% aqueous HCl
  10. extractionthe solution was extracted twice with ether
  11. extractionextracted twice with ethyl acetate
  12. washwashed with brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-315a40bfe6e449b09073326de75f3137
Source dataset
uspto-grants-1995_10
Patent number
US05459152

Reaction notes

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