Triethylamine → HCID 131718018, compound

HRID 483441Notes

Reaction equation

HRID 483441 reaction equation
[CH3:1][N:2]([CH2:14][CH2:15]O)[C:3]([C:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[S:7][N:6]=1)=[O:4].[CH3:17]S([Cl:21])(=O)=O.[F:22][C:23]1[CH:37]=[CH:36][C:26]2[C:27](C3CCNCC3)=[N:28][O:29][C:25]=2[CH:24]=1.[OH-].[Na+].[CH2:40]([N:42]([CH2:45][CH3:46])[CH2:43][CH3:44])[CH3:41]>C1(C)C=CC=CC=1>[OH2:4].[ClH:21].[CH3:1][N:2]([CH2:14][CH2:15][CH:17]1[CH2:44][CH2:43][N:42]([C:27]2[C:26]3[CH:36]=[CH:37][C:23]([F:22])=[CH:24][C:25]=3[O:29][N:28]=2)[CH2:45][CH2:46]1)[C:3]([C:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[S:7][N:6]=1)=[O:4].[CH3:1][N:2]([CH2:14][CH2:15][CH:17]1[CH2:44][CH2:43][N:42]([C:45]2[C:46]3[CH:36]=[CH:37][C:23]([F:22])=[CH:24][C:25]=3[O:29][N:28]=2)[CH2:40][CH2:41]1)[C:3]([C:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[S:7][N:6]=1)=[O:4].[ClH:21]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 10105529HCID 10105529, compound

Product 1

HCID 131718018HCID 131718018, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of N-methyl-N-(2-hydroxyethyl)-1,2-benzisothiazole-3-carboxamide (4.00 g) and triethylamine (2.48 ml), in sieve-dried toluene (100 ml) stirred at 0°, under nitrogen, was added dropwise methanesulfonyl chloride (1.34 ml). The mixture was stirred and warmed to ambient temperature. After 45 mins, 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.72 g) was added, and the mixture was heated for 18 hrs under reflux, with stirring. The mixture was allowed to cool to room temperature, and was added to 2% sodium hydroxide solution. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined extracts were washed with water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed on silica using ethyl acetate as eluent. The appropriate fractions were collected and evaporated. The residue was dissolved in dichloromethane and hydrogen chloride in ethanol was added, followed by ether. The salt was recrystallized from dichloromethane/ether to provide 1.45 g (14.0%) product, mp 211°-214° C. (dec).

Workup

  1. temperaturethe mixture was heated for 18 hrs
  2. temperatureunder reflux
  3. stirringwith stirring
  4. temperatureto cool to room temperature
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined extracts were washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated in vacuo
  11. customThe residue was chromatographed on silica
  12. customThe appropriate fractions were collected
  13. customevaporated
  14. dissolutionThe residue was dissolved in dichloromethane
  15. additionhydrogen chloride in ethanol was added
  16. customThe salt was recrystallized from dichloromethane/ether

Sources & evidence

ORD record
ord-b5e20ada573d4b43bc7b8f2ae358d7cf
Source dataset
uspto-grants-1993_07
Patent number
US05225412

Reaction notes

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