5-Thiazolecarboxylic acid, 2-methyl- → HCID 66643786, compound

HRID 1923495Notes

Reaction equation

HRID 1923495 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=1.[Li+].CC([N-]C(C)C)C.Cl[CH2:19][C:20]1[C:21]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:22][O:23][C:24]=1[CH3:25]>C1COCC1>[CH3:25][C:24]1[O:23][N:22]=[C:21]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:20]=1[CH2:19][CH2:1][C:2]1[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=1

Participants

5

Reactant 3

HCID 988455-Thiazolecarboxylic acid, 2-methyl-HCID 2724682Lithium diisopropylamideHCID 11052826Isoxazole, 4-(chloromethyl)-5-methyl-3-phenyl-

Product 1

HCID 66643786HCID 66643786, compoundYield 61.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 2-methyl-thiazole-5-carboxylic acid (100 mg, 0.7 mmol) in THF (5 mL) at −72° C. and under argon was added LDA (0.7 mL of a 2M solution in THF, 1.40 mmol) dropwise. After 1.5 h a solution of 4-chloromethyl-5-methyl-3-phenyl-isoxazole (145 mg, 0.7 mmol) in THF (5 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 then triturated with diisopropyl ether to give the title compound (135 mg, 61%) as a light brown solid which was used directly in the next reaction.

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. customthen triturated with diisopropyl ether

Sources & evidence

ORD record
ord-b36ad52c13784a4a8717eda404dbf3a3
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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