Triethylamine → N-(1-Methylethyl)-N-[2-(1-(6-fluoro-1,2-benzisoxazol-3-yl)-4-piperadinyl)ethyl]-1,2-benzisoxazol-3-carboxamide

HRID 1885319Notes

Reaction equation

HRID 1885319 reaction equation
[CH3:1]S(Cl)(=O)=O.[CH3:6][CH:7]([N:9]([CH2:21][CH2:22]O)[C:10]([C:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][N:13]=1)=[O:11])[CH3:8].[F:24][C:25]1[CH:39]=[CH:38][C:28]2[C:29](C3CCNCC3)=[N:30][O:31][C:27]=2[CH:26]=1.C([N:42]([CH2:45][CH3:46])[CH2:43][CH3:44])C>O.O1CCCC1>[CH3:8][CH:7]([N:9]([CH2:21][CH2:22][CH:1]1[CH2:44][CH2:43][N:42]([C:29]2[C:28]3[CH:38]=[CH:39][C:25]([F:24])=[CH:26][C:27]=3[O:31][N:30]=2)[CH2:45][CH2:46]1)[C:10]([C:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][N:13]=1)=[O:11])[CH3:6]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 10332255N-(1-Methylethyl)-N-(2-hydroxyethyl)-1,2-benzisoxazole-3-carboxamide

Product 1

HCID 19880304N-(1-Methylethyl)-N-[2-(1-(6-fluoro-1,2-benzisoxazol-3-yl)-4-piperadinyl)ethyl]-1,2-benzisoxazol-3-carboxamideYield 16.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, methanesulfonyl chloride (3.70 g) was rapidly added to a solution of N-(1-methylethyl)-N-(2-hydroxyethyl)-1,2-benzisoxazole-3-carboxamide (8.00 g), triethylamine (3.27 g), and tetrahydrofuran (150 ml), at 0° C., and the mixture stirred at 0° C. for 30 mins. To the mixture was added rapidly a suspension of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (7.80 g), triethylamine (6.53 g), and tetrahydrofuran (60 ml), and the mixture was heated under reflux for 12 hrs. Water was added and the solution was concentrated under reduced pressure. The residue was dissolved in dichloromethane (150 ml), washed with 10% sodium hydroxide solution, water, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with 80% ethyl acetate in hexanes. The appropriate fractions were collected and evaporated, and the residue was recrystallized from ether to afford 2.33 g (16.0%) of product, mp 118°-120° C.

Workup

  1. additionTo the mixture was added rapidly
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 12 hrs
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane (150 ml)
  6. washwashed with 10% sodium hydroxide solution, water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customThe residue was chromatographed on silica gel
  11. washeluting with 80% ethyl acetate in hexanes
  12. customThe appropriate fractions were collected
  13. customevaporated
  14. customthe residue was recrystallized from ether

Sources & evidence

ORD record
ord-8cb776ef873148d5b2238bd388bddb4f
Source dataset
uspto-grants-1992_09
Patent number
US05143923

Reaction notes

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