Acetic Acid → HCID 131724453, compound

HRID 352164Notes

Reaction equation

HRID 352164 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:4]=1[C:10]1[C:14]([C:15](Cl)=[O:16])=[C:13]([CH3:18])[O:12][N:11]=1.C([N:21]([CH2:24][CH3:25])CC)C.[C:26]([OH:29])(=O)[CH3:27]>>[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:4]=1[C:10]1[C:14]([C:15]([NH:21][CH:24]2[CH2:25][CH2:18][CH2:13][CH:14]([CH2:10][C:26](=[O:29])[CH2:27][C:8]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:15]2)=[O:16])=[C:13]([CH3:18])[O:12][N:11]=1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27365813-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride

Product 1

HCID 131724453HCID 131724453, compound

Procedure

A compound from preparation 88 (3.0 g; 9.05 mmol) was dissolved in excess, neat acetic acid saturated with HCl(g) (20 mL). After 30 min of stirring at room temperature, in air, the solution was concentrated to dryness by rotary evaporation. Acetic acid was removed from the resultant solid by consecutive dissolution in, and drying from, acetonitrile (thrice) and then diethyl ether (once). The resulting white powder was dissolved in anhydrous dichloromethane (400 mL) under a nitrogen atmosphere. First was added 3-(2-chloro-6-fluoro-phenyl)-5-methylisoxazole-4-carbonyl chloride (2.74 g; 9.99 mmol; 1.1 equiv), and then 4-N,N-dimethylaminopyridine (114 mg; 0.93 mmol; 0.1 equiv) and finally triethylamine (5 mL; 36.3 mmol; 4 equiv). The reaction solution was stirred 17 h and then quenched with saturated NaHCO3(aq). The organic layer was washed with saturated NaHCO3(aq) (twice), saturated NaCl(aq) (once), dried with Na2SO4(s), filtered, and concentrated to dryness by rotary evaporation. The resulting oil was dissolved in dichloromethane and purified by column chromatography on a 6×15 cm silica gel bed in dichloromethane. Dichloromethane (1 L) was followed by a 2% tetrahydrofuran/dichloromethane (v/v) mobile phase. A white solid (3.93 g; 95%) was obtained. TOF-MS(ES) calc'd: [M+H]+=469.1694 m/z. Found: 469.1692 m/z.

Workup

  1. customA compound from preparation 88 (3.0 g; 9.05 mmol)
  2. concentrationthe solution was concentrated to dryness by rotary evaporation
  3. customAcetic acid was removed from the resultant solid
  4. dissolutionby consecutive dissolution in, and
  5. dry with materialdrying from, acetonitrile (thrice)
  6. dissolutionThe resulting white powder was dissolved in anhydrous dichloromethane (400 mL) under a nitrogen atmosphere
  7. stirringThe reaction solution was stirred 17 h
  8. customquenched with saturated NaHCO3(aq)
  9. washThe organic layer was washed with saturated NaHCO3(aq) (twice), saturated NaCl(aq) (once),
  10. dry with materialdried with Na2SO4(s)
  11. filtrationfiltered
  12. concentrationconcentrated to dryness by rotary evaporation
  13. dissolutionThe resulting oil was dissolved in dichloromethane
  14. custompurified by column chromatography on a 6×15 cm silica gel bed in dichloromethane
  15. customA white solid (3.93 g; 95%) was obtained

Sources & evidence

ORD record
ord-687b42bf992c40779f173928b8be0e6b
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

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