Ethanolamine → 2-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide

HRID 1923616Notes

Reaction equation

HRID 1923616 reaction equation
CO[C:3]([C:5]1[S:9][C:8](/[CH:10]=[CH:11]/[C:12]2[C:13]([CH2:18][CH2:19][CH2:20][CH3:21])=[N:14][O:15][C:16]=2[CH3:17])=[N:7][C:6]=1[CH3:22])=[O:4].[CH2:23]([CH2:25][NH2:26])[OH:24]>C1(C)C=CC=CC=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>[OH:24][CH2:23][CH2:25][NH:26][C:3]([C:5]1[S:9][C:8](/[CH:10]=[CH:11]/[C:12]2[C:13]([CH2:18][CH2:19][CH2:20][CH3:21])=[N:14][O:15][C:16]=2[CH3:17])=[N:7][C:6]=1[CH3:22])=[O:4]

Participants

5

Reactant 2

HCID 700EthanolamineHCID 666436512-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid methyl ester

Product 1

HCID 497811512-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amideYield 81.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 9357Potassium Sodium TartrateSolvent

Procedure

To a stirred solution of 2-[(E)-2-(3-butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid methyl ester (Example 93c, 1.0 g, 3.12 mmol) in toluene (7 mL) was added ethanolamine (229 mg, 3.75 mmol) and TBD (261 mg, 1.88 mmol). After 22 h the reaction mixture was diluted with Seignette's salt and extracted with ethyl acetate. The combined extracts were dried, filtered and concentrated in vacuo, then purified by chromatography (silica, 0 to 10% methanol in dichloromethane) then on a 5×50 cm Chiralpak AD column at room temperature using an isopropanol:heptane (2:8) mobile phase with UV detection at 220 nM to give the less polar component 2-[(E)-2-(3-butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide (884 mg, 81%) as a pale yellow solid then the most polar component 2-[(Z)-2-(3-butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide (80 mg, 7%) as a pale yellow solid. MS: m/e=350.4 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe combined extracts were dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified by chromatography (silica, 0 to 10% methanol in dichloromethane)
  6. customat room temperature

Sources & evidence

ORD record
ord-773f6a589eb0456b9ffa6a644e65ac45
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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