Triethylamine → HCID 90202458, compound

HRID 929754Notes

Reaction equation

HRID 929754 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][O:6][C:7]1[CH:15]=[CH:14][C:10]([CH:11]=[N:12][OH:13])=[CH:9][CH:8]=1.ClN1C(=O)CCC1=O.[C:27]([O:31][CH2:32][CH3:33])(=[O:30])[C:28]#[CH:29].C(N(CC)CC)C>CN(C=O)C.CCOCC>[CH2:32]([O:31][C:27]([C:28]1[O:13][N:12]=[C:11]([C:10]2[CH:14]=[CH:15][C:7]([O:6][CH2:5][C:4]3[CH:16]=[CH:17][CH:18]=[C:2]([F:1])[CH:3]=3)=[CH:8][CH:9]=2)[CH:29]=1)=[O:30])[CH3:33]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12182Ethyl propiolateHCID 31398ChlorosuccinimideHCID 797883HCID 797883, compound2×

Product 1

HCID 90202458HCID 90202458, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-(3-Fluoro-benzyloxy)-benzaldehyde oxime (which may be prepared as described in Preparation of Intermediate 3; 2 g, 8.2 mmol) was dissolved in DMF (4.8 mL) and the solution was cooled to 0° C. in an ice-water bath. N-Chlorosuccinimide (1.09 g, 8.2 mmol) was added slowly. The reaction mixture was stirred at 0° C. for 30 min, allowed to warm to room temperature and stirred at room temperature for 1 h. The reaction mixture was poured into ice-water (125 mL) and the resulting suspension was extracted with EtOAc (200 mL). The organic extract was dried over Na2SO4, filtered, and evaporated. The residue was dissolved in Et2O (20 mL). A mixture of ethyl propiolate (1.1 mL, 10.9 mmol) and triethylamine (1.5 mL) in Et2O (20 mL) was added dropwise, and the mixture was stirred at room temperature for 9 days. Silica gel was added and the solvent was evaporated. The resulting mixture was purified by chromatography (5-15% EtOAc/hexane) to give 3-[4-(3-fluoro-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid ethyl ester (160 mg, 6%) as a white crystalline solid, which contained some of the undesired 4-carboxylic acid ethyl ester regioisomer.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred at room temperature for 1 h
  3. extractionthe resulting suspension was extracted with EtOAc (200 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in Et2O (20 mL)
  9. additionwas added dropwise
  10. stirringthe mixture was stirred at room temperature for 9 days
  11. additionSilica gel was added
  12. customthe solvent was evaporated
  13. customThe resulting mixture was purified by chromatography (5-15% EtOAc/hexane)

Sources & evidence

ORD record
ord-60bd76e5ebb54194ba18926dd6752ed7
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

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