Sodium Carbonate → 5-(2,4-Bis-benzyloxy-5-isobutyl-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamide

HRID 1891188Notes

Reaction equation

HRID 1891188 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[C:10](I)=[C:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][C:13]=2[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:8][N:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[CH:44]([C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1)=[O:45]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([NH:3][C:4]([C:6]1[C:10]([C:49]2[CH:50]=[CH:51][C:46]([CH:44]=[O:45])=[CH:47][CH:48]=2)=[C:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][C:13]=2[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:8][N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 24773447HCID 24773447, compound

Product 1

HCID 247735315-(2,4-Bis-benzyloxy-5-isobutyl-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamide

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

5-(2,4-Bis-benzyloxy-5-isobutyl-phenyl)-4-iodo-isoxazole-3-carboxylic acid ethylamide (1 eq) was dissolved in DMF and 1M Na2CO3 (aq) (3 eq) was added, followed by 4-formylphenylboronic acid (2 eq) and catalytic PdCl2(PPh3)2. Nitrogen was bubbled through the solution for ten minutes at ambient temperature, after which time, the temperature was elevated to 80° C. under a nitrogen atmosphere, for 2 hours. The reaction mixture was allowed to cool to room temperature and the reaction mixture was diluted with ethyl acetate. This solution was washed with brine, then dried over magnesium sulfate, filtered and concentrated in vacuo to give an oil which was purified by column chromatography, eluting with 10% EtOAc in hexane, to give 5-(2,4-bis-benzyloxy-5-isobutyl-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamide as a white solid.

Workup

  1. customNitrogen was bubbled through the solution for ten minutes at ambient temperature
  2. additionthe reaction mixture was diluted with ethyl acetate
  3. washThis solution was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil which
  8. customwas purified by column chromatography
  9. washeluting with 10% EtOAc in hexane

Sources & evidence

ORD record
ord-f7e04c89db904afab982f983c936233d
Source dataset
uspto-grants-2013_08
Patent number
US08507480B2

Reaction notes

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