Trimethylaluminum → (s)-4-Methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid (tetrahydro-furan-3-yl)-amide

HRID 1923490Notes

Reaction equation

HRID 1923490 reaction equation
Cl.[O:2]1[CH2:6][CH2:5][C@H:4]([NH2:7])[CH2:3]1.C[Al](C)C.[CH3:12][C:13]1[N:14]=[C:15]([CH2:21][CH2:22][C:23]2[C:24]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:25][O:26][C:27]=2[CH3:28])[S:16][C:17]=1[C:18](O)=[O:19]>C1(C)C=CC=CC=1>[O:2]1[CH2:6][CH2:5][C@H:4]([NH:7][C:18]([C:17]2[S:16][C:15]([CH2:21][CH2:22][C:23]3[C:24]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[N:25][O:26][C:27]=3[CH3:28])=[N:14][C:13]=2[CH3:12])=[O:19])[CH2:3]1

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 18664284(3S)-oxolan-3-amine hydrochlorideHCID 66643564HCID 66643564, compound

Product 1

HCID 49782926(s)-4-Methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid (tetrahydro-furan-3-yl)-amideYield 45.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
90 °C

Procedure

To a stirred suspension of (S)-tetrahydrofuran-3-amine HCl (127 mg, 1.0 mmol) in toluene (2 mL) under argon at room temperature was added trimethylaluminium (1 mL of a 2M solution in toluene, 2.0 mmol). After 2 h, a solution of 4-methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid (130 mg, 0.39 mmol) in toluene (4 mL) was added and the reaction mixture warmed to 90° C. After 2 h, the reaction mixture was cooled, quenched with ice water and extracted with dichloromethane. The combined extracts were washed with Seignette's salt solution then dried, filtered, and concentrated. Purification by chromatography (silica, 0 to 10% methanol in dichloromethane) gave the title compound (71 mg, 45%) as a colourless oil. MS: m/e=398.1 [M+H]+.

Workup

  1. waitAfter 2 h
  2. temperaturethe reaction mixture was cooled
  3. customquenched with ice water
  4. extractionextracted with dichloromethane
  5. washThe combined extracts were washed with Seignette's salt solution
  6. customthen dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by chromatography (silica, 0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0b0ecb4c038149969980bd3d723f020d
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

Loading…