Dimethyl-1,3-thiazole-5-carboxylic acid → 2-{2-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-2-hydroxy-ethyl}-4-methyl-thiazole-5-carboxylic acid

HRID 1923573Notes

Reaction equation

HRID 1923573 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])=[C:26]([CH3:30])[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)=[C:26]([CH3:30])[O:25][N:24]=2)=[N:21][CH:22]=1

Participants

5

Reactant 3

HCID 736488Dimethyl-1,3-thiazole-5-carboxylic acidHCID 866472723-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 666437052-{2-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-2-hydroxy-ethyl}-4-methyl-thiazole-5-carboxylic acidYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2,4-dimethyl-thiazole-5-carboxylic acid (650 mg, 7.0 mmol) in THF (33 mL) at −70° C. and under argon was added BuLi (1.6M in hexanes, 4.94 mL, 7.9 mmol) dropwise. After 2 h a solution of 3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazole-4-carbaldehyde (814 mg, 3.95 mmol) in THF (12 mL) was added dropwise. After 2 h the reaction mixture was quenched with citric acid solution (5%, 25 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 (729 mg, 51%) as a light yellow solid. MS: m/e=362.2 [M+H]+.

Workup

  1. customAfter 2 h the reaction mixture was quenched with citric acid solution (5%, 25 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-07c00ccfa2b840d5a9a28440a16892b1
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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