Dimethylformamide → 5-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamide

HRID 2097267Notes

Reaction equation

HRID 2097267 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[C:10](I)=[C:9]([C:12]2[CH:17]=[C:16]([Cl:18])[C:15]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:14][C:13]=2[O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:8][N:7]=1)=[O:5])[CH3:2].[C:35]([O-:38])(O)=O.[Na+].CN(C=O)C>CCOC(C)=O.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:12]2[CH:17]=[CH:16][C:15]([CH:35]=[O:38])=[CH:14][CH:13]=2)=[C:9]([C:12]2[CH:17]=[C:16]([Cl:18])[C:15]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:14][C:13]=2[O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:8][N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 592647675-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-iodo-isoxazole-3-carboxylic acid ethylamide

Product 1

HCID 247741115-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamideYield 163.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

5-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-iodo-isoxazole-3-carboxylic acid ethylamide (prepared as for Example 31) (2 g, 3.4 mmol), 4-formylboronic acid (0.612 g, 4.08 mmol), NaHCO3 (10.2 ml, 1M aq. solution, 10.2 mmol), PdCl2(PPh3)2 (119 mg, 0.17 mmol) and DMF (50 ml) were combined. The mixture was then degassed by bubbling N2 through it for 5 minutes before being heated at 80° C. for 1 hour. The mixture was then evaporated in vacuo and partitioned between EtOAc (3×50 ml) and water (50 ml). The combined, dried (Na2SO4) organics were evaporated in vacuo to give a crude oil. This was dissolved in EtOAc and passed through a plug of SiO2, washing through with EtOAc. The filtrate was evaporated in vacuo and the resulting oil triturated with Et2O to afford 5-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamide (1.577 g, 82%) as a pale coloured solid, LC/MS: RT=2.908 min. 567.3 (MH+).

Workup

  1. customThe mixture was then degassed
  2. customby bubbling N2 through it for 5 minutes
  3. customThe mixture was then evaporated in vacuo
  4. custompartitioned between EtOAc (3×50 ml) and water (50 ml)
  5. dry with materialdried (Na2SO4)
  6. customorganics were evaporated in vacuo
  7. customto give a crude oil
  8. washwashing through with EtOAc
  9. customThe filtrate was evaporated in vacuo
  10. customthe resulting oil triturated with Et2O

Sources & evidence

ORD record
ord-d2c573133fc34fa0abc8add8a241e2c9
Source dataset
uspto-grants-2013_05
Patent number
US08450310B2

Reaction notes

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