5-(2,4-Bis-benzyloxy-5-styrylphenyl)-isoxazole-3-carboxylic acid ethylamide → 5-(2,4-Bis-benzyloxy-5-phenethylphenyl)-isoxazole-3-carboxylic acid ethylamide

HRID 1891159Notes

Reaction equation

HRID 1891159 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[C:15]([CH:17]=[CH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:13][C:12]=2[O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:8][N:7]=1)=[O:5])[CH3:2]>[Pd].O1CCOCC1>[CH2:1]([NH:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[C:15]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:13][C:12]=2[O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:8][N:7]=1)=[O:5])[CH3:2]

Participants

4

Reactant 1

HCID 667588525-(2,4-Bis-benzyloxy-5-styrylphenyl)-isoxazole-3-carboxylic acid ethylamide

Product 1

HCID 247733535-(2,4-Bis-benzyloxy-5-phenethylphenyl)-isoxazole-3-carboxylic acid ethylamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

Palladium on charcoal catalyst (10%; 50 mg) was added to a degassed solution of 5-(2,4-Bis-benzyloxy-5-styrylphenyl)-isoxazole-3-carboxylic acid ethylamide (690 mg, 1.30 mmol) in 1,4-dioxane (50 mL) under a nitrogen atmosphere. The reaction mixture was hydrogenated for a total of 4.75 hrs with further Pd on charcoal catalyst (50 mg) added at 0.75 and 2.5 hrs. The reaction mixture was filtered through a pad of celite, which was washed with 1,4-dioxane (20 mL) and dichloromethane (20 mL). The combined filtrate solvents were removed in vacuo to afford a cream-coloured solid, which was purified by flash chromatography on silica gel (20 g, IST) eluting with 10 to 50% ethyl acetate in hexane. This affords 5-(2,4-Bis-benzyloxy-5-phenethylphenyl)-isoxazole-3-carboxylic acid ethylamide as a pale yellow solid (609 mg, 88%). LCMS: [M+H]+ 533. 1H NMR (400 MHz, CDCl3) 1.26 (t, 3H), 2.86-2.96 (m, 4H), 3.49 (m, 2H), 5.03 (s, 2H), 5.18 (s, 2H), 6.56 (s, 1H), 6.81 (t, 1H), 7.07 (s, 1H), 7.15-7.20 (m, 3H), 7.23-7.28 (m, 2H), 7.31-7.42 (m, 10H), 7.73 (s, 1H).

Workup

  1. additionadded at 0.75 and 2.5 hrs
  2. filtrationThe reaction mixture was filtered through a pad of celite, which
  3. washwas washed with 1,4-dioxane (20 mL) and dichloromethane (20 mL)
  4. customThe combined filtrate solvents were removed in vacuo
  5. customto afford a cream-coloured solid, which
  6. customwas purified by flash chromatography on silica gel (20 g, IST)
  7. washeluting with 10 to 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-75598a09852c4a4caaab9acd74651cea
Source dataset
uspto-grants-2013_08
Patent number
US08507480B2

Reaction notes

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