Dimethyl-1,3-thiazole-5-carboxylic acid → HCID 66643633, compound

HRID 1923600Notes

Reaction equation

HRID 1923600 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5]([CH3:7])[N:6]=1.[Li]CCCC.[F:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:27]([CH:28]=[O:29])=[CH:26][O:25][N:24]=2)=[N:21][CH:22]=1>C1COCC1>[F:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:27]([CH:28]([OH:29])[CH2:1][C:2]3[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5]([CH3:7])[N:6]=3)=[CH:26][O:25][N:24]=2)=[N:21][CH:22]=1

Participants

5

Reactant 3

HCID 736488Dimethyl-1,3-thiazole-5-carboxylic acidHCID 866472733-(5-Fluoro-pyridin-2-yl)-isoxazole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 66643633HCID 66643633, compoundYield 55.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2,4-dimethyl-thiazole-5-carboxylic acid (1.36 g, 8.63 mmol) in THF (72 mL) at −70° C. and under argon was added BuLi (1.6M in hexanes, 10.8 mL, 17.27 mmol) dropwise. After 2 h a solution of 3-(5-fluoro-pyridin-2-yl)-isoxazole-4-carbaldehyde (1.78 g, 8.63 mmol) in THF (26 mL) was added dropwise. After 1 h the reaction mixture was quenched with citric acid solution (5%, 55 mL) then warmed to room temperature and extracted with ethyl acetate. The combined extracts were washed with brine, water, dried over sodium sulfate, filtered and concentrated. Purification by recrystallization (ethyl acetate) afforded the title compound (1.67 g, 55%) as a light yellow solid. MS: m/e=348.2 [M−H]−.

Workup

  1. customAfter 1 h the reaction mixture was quenched with citric acid solution (5%, 55 mL)
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with brine, water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification
  8. customby recrystallization (ethyl acetate)

Sources & evidence

ORD record
ord-6fc7042321a643418103ddab87af1d3e
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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