Water → 2-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-thiazole-5-carboxylic acid ethyl ester

HRID 1923639Notes

Reaction equation

HRID 1923639 reaction equation
[H-].[Na+].[CH3:3][C:4]1[O:8][N:7]=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]=1[CH2:15][OH:16].[CH2:17]([O:19][C:20]([C:22]1[S:26][C:25](Cl)=[N:24][CH:23]=1)=[O:21])[CH3:18].O>O1CCCC1>[CH2:17]([O:19][C:20]([C:22]1[S:26][C:25]([O:16][CH2:15][C:5]2[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N:7][O:8][C:4]=2[CH3:3])=[N:24][CH:23]=1)=[O:21])[CH3:18]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2776149(5-Methyl-3-phenyl-1,2-oxazol-4-yl)methanolHCID 19017727Ethyl 2-chloro-1,3-thiazole-5-carboxylate

Product 1

HCID 595684942-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-thiazole-5-carboxylic acid ethyl esterYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of sodium hydride (304 mg, 6.98 mmol, 60% dispersion in mineral oil) in tetrahydrofuran (30 mL) at 0° C. under argon was added (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (1.0 g, 5.28 mmol) The mixture was warmed to room temperature and after 1 h the reaction mixture was cooled to 0° C. then a solution of 2-chloro-thiazole-5-carboxylic acid ethyl ester (1.01 g, 5.28 mmol) in THF (15 mL) added. The reaction mixture was warmed to room temperature and after 15 h, water (20 mL) was added and the resulting mixture extracted with ethyl acetate. The combined organic extracts were dried, filtered and concentrated. Purification by chromatography (silica, 20% ethyl acetate in heptane) gave the title compound (940 mg, 52% yield) as an off-white solid. MS: m/e=345.0 [M+H]+.

Workup

  1. temperaturewas cooled to 0° C.
  2. temperatureThe reaction mixture was warmed to room temperature and after 15 h
  3. extractionthe resulting mixture extracted with ethyl acetate
  4. customThe combined organic extracts were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by chromatography (silica, 20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e204716e625e4753843b7c04b8808360
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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