Dimethyl-1,3-thiazole-5-carboxylic acid → HCID 66643786, compound

HRID 1923488Notes

Reaction equation

HRID 1923488 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=[O:9])=[C:5](C)[N:6]=1.[Li+].CC([N-]C(C)C)C.Cl[CH2:20][C:21]1[C:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[N:23][O:24][C:25]=1[CH3:26]>C1COCC1>[CH3:26][C:25]1[O:24][N:23]=[C:22]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:21]=1[CH2:20][CH2:1][C:2]1[S:3][C:4]([C:8]([OH:10])=[O:9])=[CH:5][N:6]=1

Participants

5

Reactant 3

HCID 736488Dimethyl-1,3-thiazole-5-carboxylic acidHCID 2724682Lithium diisopropylamideHCID 11052826Isoxazole, 4-(chloromethyl)-5-methyl-3-phenyl-

Product 1

HCID 66643786HCID 66643786, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 2,4-dimethyl-thiazole-5-carboxylic acid (250 mg, 1.59 mmol) in THF (16 mL) at −78° C. and under argon was added LDA (1.6 mL of a 2M solution in THF, 3.2 mmol) dropwise. After 1.5 h a solution of 4-chloromethyl-5-methyl-3-phenyl-isoxazole (330 mg, 1.59 mmol) in THF (4 mL) was added dropwise. After 1 h the reaction mixture was quenched with HCl (1N, 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 (315 mg, 60%) as a light yellow gum. MS: m/e=329.1 [M+H]+.

Workup

  1. customAfter 1 h the reaction mixture was quenched with HCl (1N, 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-c5e805334f854520b6753a3e2cade8ce
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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