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

HRID 1363711Notes

Reaction equation

HRID 1363711 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 16 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.1 The crude product was dissolved in a small amount of DCM and purified by flash chromatography (heptane/EtOAc 2:1->1:2). Fractions containing the product were pooled and evaporated to a product (ca 14 g) containing impurities of DDT. The crude product was dissolved in diethyl ether (100 mL) and washed with water eight times. The ether phase was dried (MgSO4), filtered and evaporated to give 8.45 g (54%) of 95% pure 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester as light brown crystals. 1As the DTT impurities is not easily removed by flash chromatography it's recommended that the crude product is dissolved in Et2O and subsequently washed with water several times at then purified by flash chromatography.

Workup

  1. stirringthe reaction mixture was stirred for further 16 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. dissolutionevaporated.1 The crude product was dissolved in a small amount of DCM
  8. custompurified by flash chromatography (heptane/EtOAc 2:1->1:2)
  9. additionFractions containing the product
  10. customevaporated to a product (ca 14 g)
  11. additioncontaining impurities of DDT
  12. dissolutionThe crude product was dissolved in diethyl ether (100 mL)
  13. washwashed with water eight times
  14. dry with materialThe ether phase was dried (MgSO4)
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-10d1427de3f54079aeee3a8bb0c4b10e
Source dataset
uspto-grants-2011_02
Patent number
US07884210B2

Reaction notes

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