Potassium Carbonate → Ethyl 2-[(2-amino-1,3-thiazol-5-yl)sulfanyl]-2-methylpropanoate

HRID 1095419Notes

Reaction equation

HRID 1095419 reaction equation
[S:1]([C:4]1[S:8][C:7]([NH2:9])=[N:6][CH:5]=1)C#N.C(S)[C@@H](O)[C@@H](O)CS.[CH2:18]([O:20][C:21](=[O:26])[C:22](Br)([CH3:24])[CH3:23])[CH3:19].C([O-])([O-])=O.[K+].[K+]>CO.CCOC(C)=O.O>[CH2:18]([O:20][C:21](=[O:26])[C:22]([S:1][C:4]1[S:8][C:7]([NH2:9])=[N:6][CH:5]=1)([CH3:24])[CH3:23])[CH3:19]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 439352DithioerythritolHCID 3109677[(2-Amino-1,3-thiazol-5-yl)sulfanyl]formonitrile

Product 1

HCID 57481427Ethyl 2-[(2-amino-1,3-thiazol-5-yl)sulfanyl]-2-methylpropanoateYield 53.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a nitrogen atmosphere 5-thiocyanato-thiazol-2-ylamine (10 g, 64 mmol) dissolved in MeOH (300 mL) was added 2,3-dihydroxy-1,4-dithiolbutane (DTT, 9.8 g, 64 mmol) and stirred at room temperature for 1½ h. Then 2-bromo-2-methyl-propionic acid ethyl ester (13.6 g, 70 mmol) and K2CO3 (10.5 g, 76 mmol) was added and the reaction mixture was stirred for further 13 h. Addition of water (500 mL) and EtOAc (500 mL). Separation of the organic phase followed by extraction of the aqueous phase with EtOAc (2×300 mL). The combined organic phases were washed with water (500 mL) and brine (2×400 mL) and dried (MgSO4), filtered and evaporated. The crude product was dissolved in a small amount of DCM and purified by flash chromathography (heptane/EtOAc 2:1->1:2). Fractions containing the product were pooled and evaporated to a product containing impurities of DDT. This product was dissolved in diethyl ether (100 mL) and washed with water several times. The ether phase was dried (MgSO4), filtered and evaporated to give 8.45 g (54%) of 95% pure 2-(2-aminothiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester as light brown crystals.

Workup

  1. stirringthe reaction mixture was stirred for further 13 h
  2. customSeparation of the organic phase
  3. extractionfollowed by extraction of the aqueous phase with EtOAc (2×300 mL)
  4. washThe combined organic phases were washed with water (500 mL) and brine (2×400 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe crude product was dissolved in a small amount of DCM
  9. custompurified by flash chromathography (heptane/EtOAc 2:1->1:2)
  10. additionFractions containing the product
  11. customevaporated to a product
  12. additioncontaining impurities of DDT
  13. dissolutionThis product was dissolved in diethyl ether (100 mL)
  14. washwashed with water several times
  15. dry with materialThe ether phase was dried (MgSO4)
  16. filtrationfiltered
  17. customevaporated

Sources & evidence

ORD record
ord-129a64c7e899411d9aab5fd864af3702
Source dataset
uspto-grants-2012_03
Patent number
US08138185B2

Reaction notes

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