3-Bromopyridine → Pyridin-3-yl(thiazol-5-yl)methanone

HRID 928736

Reaction equation

HRID 928736 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.CON(C)[C:16]([C:18]1[S:22][CH:21]=[N:20][CH:19]=1)=[O:17]>CCOCC>[N:9]1[CH:10]=[CH:11][CH:12]=[C:7]([C:16]([C:18]2[S:22][CH:21]=[N:20][CH:19]=2)=[O:17])[CH:8]=1

Participants

5

Reactant 3

HCID 122863-BromopyridineHCID 25307138N-Methoxy-N-methyl-1,3-thiazole-5-carboxamideHCID 178418339Butyllithium

Product 1

HCID 80477200Pyridin-3-yl(thiazol-5-yl)methanone

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

A n-BuLi solution (2.37 mL, 3.80 mmol, 1.6 M solution in hexane) was slowly added to a −78° C. to a solution of 3-bromopyridine (0.600 g, 3.80 mmol) in Et2O (10 mL). After addition, stirring was continued for an additional 40 minutes and N-methoxy-N-methylthiazole-5-carboxamide (0.752 g, 4.37 mmol, Intermediate 11: step a) dissolved in Et2O (10 mL) was slowly added. The mixture was stirred at −78° C. for 10 minutes then warmed to 0° C. and stirred for 1 hour. The cold solution was quenched with saturated aqueous NH4Cl and warmed to room temperature. H2O was added and layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts washed with brine, dried over Na2SO4, filtered, evaporated in vacuo and chromatographed (CH2Cl2/EtOAc) to provide the title compound as a yellow solid (precipitated from Et2O and dried under reduced pressure).

Workup

  1. additionAfter addition
  2. additionwas slowly added
  3. stirringThe mixture was stirred at −78° C. for 10 minutes
  4. stirringstirred for 1 hour
  5. customThe cold solution was quenched with saturated aqueous NH4Cl
  6. temperaturewarmed to room temperature
  7. additionH2O was added
  8. customlayers were separated
  9. extractionThe aqueous layer was extracted with EtOAc
  10. washthe combined organic extracts washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. customchromatographed (CH2Cl2/EtOAc)

Sources & evidence

ORD record
ord-bfe976336310436f882f722621c6fc03
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Linked notes

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