Dimethylformamide → HCID 76282127, compound

HRID 929820Notes

Reaction equation

HRID 929820 reaction equation
[Cl:1]N1C(=O)CCC1=O.[F:9][C:10]([F:29])([F:28])[C:11]1[CH:27]=[CH:26][CH:25]=[CH:24][C:12]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([CH:19]=[N:20][OH:21])=[CH:17][CH:16]=1.C(O[CH2:35][CH3:36])(=O)C#C.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].C[N:51]([CH:53]=[O:54])C>S([O-])([O-])(=O)=O.[Cu+2]>[Cl:1][C:16]1[CH:17]=[C:18]([C:19]2[CH:36]=[C:35]([C:53]([NH2:51])=[O:54])[O:21][N:20]=2)[CH:22]=[CH:23][C:15]=1[O:14][CH2:13][C:12]1[CH:24]=[CH:25][CH:26]=[CH:27][C:11]=1[C:10]([F:28])([F:29])[F:9]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 12182Ethyl propiolateHCID 31398ChlorosuccinimideHCID 23667548Sodium AscorbateHCID 131735127HCID 131735127, compound2×

Product 1

HCID 76282127HCID 76282127, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 24462Copper SulfateCatalyst

Procedure

N-Chlorosuccinimide (1.82 g, 13.7 mmol) was added in portions to a solution of 4-(2-trifluoromethyl-benzyloxy)-benzaldehyde oxime (which may be prepared as described in Preparation of Intermediate 21; 3.5 g, 11.9 mmol) in DMF (7 mL) at 0° C. The reaction mixture was allowed to warm to room temperature during the addition and then stirred for 2 h at room temperature. The mixture was poured into ice-water and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and evaporated. The residue was dissolved in 50% aqueous tert-butanol (90 mL). Ethyl propiolate (1.2 mL, 11.8 mmol) was added, followed by 1 M sodium ascorbate (1.23 mL, 1.23 mmol) and 0.1 M copper(II) sulfate (120 mL, 12 mmol). KHCO3 (3.75 g, 37.5 mmol) was added and the reaction mixture was stirred at room temperature for 3 h. The solid was filtered off and dissolved in 2 M NH3 in EtOH (15 mL). The resulting mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was purified by chromatography (35-40% EtOAc/hexanes) to give 3-[3-chloro-4-(2-trifluoromethyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (158 mg, 6%) as a white solid. HRMS Calcd. for C18H13ClF3N2O3 (M+H)+, 397.0562. Found: 397.0558.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe residue was dissolved in 50% aqueous tert-butanol (90 mL)
  6. stirringthe reaction mixture was stirred at room temperature for 3 h
  7. filtrationThe solid was filtered off
  8. dissolutiondissolved in 2 M NH3 in EtOH (15 mL)
  9. stirringThe resulting mixture was stirred at room temperature overnight
  10. customThe solvent was evaporated
  11. customthe residue was purified by chromatography (35-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3a05b06b824f4419aaf39eb11077bbbd
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

Loading…