5-Thiazolecarboxylic acid, 2-methyl- → HCID 66643644, compound

HRID 1923553Notes

Reaction equation

HRID 1923553 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=1.[CH2:10]([Li])CCC.[CH2:15]([C:19]1[C:23]([CH2:24]Cl)=[C:22]([CH3:26])[O:21][N:20]=1)[CH2:16][CH2:17][CH3:18]>C1COCC1.CCCCCC>[CH3:10][O:8][C:7]([C:4]1[S:3][C:2]([CH2:1][CH2:24][C:23]2[C:19]([CH2:15][CH2:16][CH2:17][CH3:18])=[N:20][O:21][C:22]=2[CH3:26])=[N:6][CH:5]=1)=[O:9]

Participants

6

Reactant 3

HCID 988455-Thiazolecarboxylic acid, 2-methyl-HCID 66643618HCID 66643618, compoundHCID 178418339Butyllithium

Product 1

HCID 66643644HCID 66643644, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a stirred solution of 2-methyl-thiazole-5-carboxylic acid (286 mg, 2.0 mmol) in THF (14 mL) at −72° C. and under argon was added n-butyllithium (2.50 mL of a 1.6M solution in hexane, 4.0 mmol) dropwise. After 2 h, a solution of 3-butyl-4-chloromethyl-5-methyl-isoxazole (375 mg, 2.0 mmol) in THF (6 mL) was added dropwise. After 2.5 h the reaction mixture was quenched with 10% aqueous citric acid (10 mL) then warmed to room temperature. The reaction mixture was extracted with ethyl acetate then the combined extracts were dried, filtered and concentrated. The resultant oil was dissolved in methanol (15 mL) and ether (7 mL) then (trimethylsilyl)diazomethane (3 mL of a 2M solution in ether, 6.0 mmol) was added dropwise. After 30 min, further (trimethylsilyl)diazomethane (3 mL of a 2M solution in ether, 6.0 mmol) was added. After 15 h, the reaction mixture was quenched with acetic acid (3 drops) then was concentrated and purified by chromatography (silica, 0 to 75% ethyl acetate in heptane) to give the title compound (360 mg, 58%) was a light brown oil. MS: m/e=309.2 [M+H]+.

Workup

  1. customAfter 2.5 h the reaction mixture was quenched with 10% aqueous citric acid (10 mL)
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. customthe combined extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resultant oil was dissolved in methanol (15 mL)
  7. additionether (7 mL) then (trimethylsilyl)diazomethane (3 mL of a 2M solution in ether, 6.0 mmol) was added dropwise
  8. waitAfter 30 min
  9. additionfurther (trimethylsilyl)diazomethane (3 mL of a 2M solution in ether, 6.0 mmol) was added
  10. waitAfter 15 h
  11. customthe reaction mixture was quenched with acetic acid (3 drops)
  12. concentrationthen was concentrated
  13. custompurified by chromatography (silica, 0 to 75% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-b2df3dd6ee604cac9340cbbf9c6ca158
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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