Dimethyl-1,3-thiazole-5-carboxylic acid → 2-[2-(3-Butyl-5-methyl-isoxazol-4-yl)-ethyl]-4-methyl-thiazole-5-carboxylic acid

HRID 1923542Notes

Reaction equation

HRID 1923542 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+].CC([N-]C(C)C)C.[CH2:19]([C:23]1[C:27]([CH2:28]Cl)=[C:26]([CH3:30])[O:25][N:24]=1)[CH2:20][CH2:21][CH3:22]>C1COCC1>[CH2:19]([C:23]1[C:27]([CH2:28][CH2:1][C:2]2[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5]([CH3:7])[N:6]=2)=[C:26]([CH3:30])[O:25][N:24]=1)[CH2:20][CH2:21][CH3:22]

Participants

5

Reactant 3

HCID 736488Dimethyl-1,3-thiazole-5-carboxylic acidHCID 2724682Lithium diisopropylamideHCID 66643618HCID 66643618, compound

Product 1

HCID 666436692-[2-(3-Butyl-5-methyl-isoxazol-4-yl)-ethyl]-4-methyl-thiazole-5-carboxylic acidYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 2,4-dimethyl-thiazole-5-carboxylic acid (157 mg, 1.0 mmol) in THF (3 mL) at −78° C. and under argon was added LDA (1.0 mL of a 2M solution in THF, 2.0 mmol) dropwise. After 1.5 h a solution of 3-butyl-4-chloromethyl-5-methyl-isoxazole (188 mg, 1.0 mmol) in THF (2 mL) was added dropwise. After 1 h the reaction mixture was quenched with HCl (1 N, 10 mL) then warmed to room temperature and extracted with ethyl acetate. The combined extracts were dried, filtered and concentrated. Purification by chromatography (silica, 0 to 10% methanol in dichloromethane) gave the title compound (210 mg, 68%) as an off white solid. MS: m/e=307.3 [M+H]+.

Workup

  1. customAfter 1 h the reaction mixture was quenched with HCl (1 N, 10 mL)
  2. extractionextracted with ethyl acetate
  3. customThe combined extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by chromatography (silica, 0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fad7cd87b78c4bd0ac9d72cf5c5b1e70
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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