Formamide → [2,4']Bithiazolyl-5'-yl-acetic acid ethyl ester

HRID 895579Notes

Reaction equation

HRID 895579 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][CH:6](Br)[C:7](=O)[C:8]1[S:9][CH:10]=[CH:11][N:12]=1)[CH3:2].[CH:16]([NH2:18])=[S:17].C(N)=O.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S>O1CCOCC1>[CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[S:17][CH:16]=[N:18][C:7]=1[C:8]1[S:9][CH:10]=[CH:11][N:12]=1)[CH3:2]

Participants

6

Reactant 4

HCID 713FormamideHCID 14817Phosphorus sulfide (P2S5)HCID 3005587MethanethioamideHCID 865876163-Bromo-4-oxo-4-thiazol-2-yl-butyric acid ethyl ester

Product 1

HCID 68497464[2,4']Bithiazolyl-5'-yl-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 3-bromo-4-oxo-4-thiazol-2-yl-butyric acid ethyl ester (2.2 g, 7.53 mmol) in 1,4-dioxane (40 mL) is added thioformamide (freshly made from formamide and P2S5 in 1,4-dioxane) (22.59 mmol). The mixture is refluxed overnight. The solvent is removed and NaHCO3 (aq.) (40 mL) and DCM (100 mL) are added to the residue. The organic layer is separated and the aqueous layer is extracted with DCM (2×40 mL). The combined organic layers are dried and solvent removed. The crude is purified by column (1% methanol n DCM) to give [2,4′]bithiazolyl-5′-yl-acetic acid ethyl ester.

Workup

  1. temperatureThe mixture is refluxed overnight
  2. customThe solvent is removed
  3. additionNaHCO3 (aq.) (40 mL) and DCM (100 mL) are added to the residue
  4. customThe organic layer is separated
  5. extractionthe aqueous layer is extracted with DCM (2×40 mL)
  6. customThe combined organic layers are dried
  7. customsolvent removed
  8. customThe crude is purified by column (1% methanol n DCM)

Sources & evidence

ORD record
ord-b0093c8efa9441f4bda0fdc3d5b1ae2d
Source dataset
uspto-grants-2005_07
Patent number
US06916819B2

Reaction notes

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