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

HRID 1594109Notes

Reaction equation

HRID 1594109 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-2bf656b9b9fb44fbba7419bf34fac344
Source dataset
uspto-grants-2007_11
Patent number
US07300945B2

Reaction notes

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