Triethylamine → HCID 131717514, compound

HRID 483443Notes

Reaction equation

HRID 483443 reaction equation
[CH3:1][CH:2]([N:4]([CH2:16][CH2:17][CH2:18]O)[C:5]([C:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][N:8]=1)=[O:6])[CH3:3].[CH3:20]S([Cl:24])(=O)=O.[ClH:25].[F:26][C:27]1[CH:40]=[CH:39][C:30]([C:31](C2CCNCC2)=[O:32])=[CH:29][CH:28]=1.C([N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])C>C1(C)C=CC=CC=1>[OH2:6].[ClH:24].[CH3:3][CH:2]([N:4]([CH2:16][CH2:17][CH2:18][CH:20]1[CH2:45][CH2:44][N:43]([C:31](=[O:32])[C:30]2[CH:29]=[CH:28][C:27]([F:26])=[CH:40][CH:39]=2)[CH2:46][CH2:47]1)[C:5]([C:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][N:8]=1)=[O:6])[CH3:1].[CH3:3][CH:2]([N:4]([CH2:16][CH2:17][CH2:18][CH:20]1[CH2:45][CH2:44][N:43]([C:31](=[O:32])[C:30]2[CH:29]=[CH:28][C:27]([F:26])=[CH:40][CH:39]=2)[CH2:46][CH2:47]1)[C:5]([C:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][N:8]=1)=[O:6])[CH3:1].[ClH:25]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 10038342HCID 10038342, compound

Product 1

HCID 131717514HCID 131717514, compoundYield 15.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(1-methylethyl)-N-(3-hydroxypropyl)-1,2-benzisoxazole-3-carboxamide (7.80 g), triethylamine (3.05 g), and toluene (200 ml), under a nitrogen atmosphere at 0° C., methanesulfonyl chloride (3.40 g), was added rapidly and the mixture was stirred at 0° C. After 35 mins, 4-(4-fluorobenzoyl)piperidine hydrochloride (7.95 g) and triethylamine (8.71 g) were added, and the mixture was heated under reflux for 16 hrs. The reaction mixture was washed with 10% sodium hydroxide, water, and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was chromatographed on silica gel, eluting with 5 to 10% methanol in ethyl acetate. The appropriate fractions were collected and evaporated. A solution of the residue in methanol was acidified with hydrogen chloride-ethanol solution and diluted with ether. The mixture was refrigerated, and the solid was collected. Recrystallization of the solid from ethanol/ethyl acetate afforded 1.50 g (10.2%) of product, mp 177°-179° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 16 hrs
  3. washThe reaction mixture was washed with 10% sodium hydroxide, water, and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was chromatographed on silica gel
  8. washeluting with 5 to 10% methanol in ethyl acetate
  9. customThe appropriate fractions were collected
  10. customevaporated
  11. additiondiluted with ether
  12. customthe solid was collected
  13. customRecrystallization of the solid from ethanol/ethyl acetate

Sources & evidence

ORD record
ord-81825d40cee847cd99ffdd2182776274
Source dataset
uspto-grants-1993_07
Patent number
US05225412

Reaction notes

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