Triethylamine → HCID 19752291, compound

HRID 483442Notes

Reaction equation

HRID 483442 reaction equation
[CH3:1]S(Cl)(=O)=O.[CH3:6][N:7]([CH2:19][CH2:20]O)[C:8]([C:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[O:12][N:11]=1)=[O:9].[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.C([N:40]([CH2:43][CH3:44])[CH2:41][CH3:42])C>O.O1CCCC1>[CH3:6][N:7]([CH2:19][CH2:20][CH:1]1[CH2:42][CH2:41][N:40]([C:27]2[C:26]3[CH:36]=[CH:37][C:23]([F:22])=[CH:24][C:25]=3[O:29][N:28]=2)[CH2:43][CH2:44]1)[C:8]([C:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[O:12][N:11]=1)=[O:9]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 10013727HCID 10013727, compound

Product 1

HCID 19752291HCID 19752291, compoundYield 22.1%

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-methyl-N-(2-hydroxyethyl)-1,2-benzisoxazole-3-carboxamide (7.10 g), triethylamine (3.27 g), and tetrahydrofuran (100 ml) at 0° C., and the mixture was stirred at 0° C. for 60 mins. To the mixture was rapidly added a suspension of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (8.10 g), triethylamine (7.26 g), and tetrahydrofuran (80 ml), and the mixture was heated under reflux for 16 hrs. Water was added, and the solution was concentrated under reduced pressure. The residue was diluted with 10% sodium hydroxide solution and extracted with 50% ether-toluene. The combined extracts were washed with water and brine, dried over anhydrous potassium carbonate, filtered, and the filtrate was concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with ethyl acetate. The appropriate fractions were collected and evaporated. The residue was recrystallized from ether to afford 3.01 g (22.1%) of product, mp 94°-97° C.

Workup

  1. additionTo the mixture was rapidly added
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 16 hrs
  4. concentrationthe solution was concentrated under reduced pressure
  5. additionThe residue was diluted with 10% sodium hydroxide solution
  6. extractionextracted with 50% ether-toluene
  7. washThe combined extracts were washed with water and brine
  8. dry with materialdried over anhydrous potassium carbonate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was chromatographed on silica gel eluting with ethyl acetate
  12. customThe appropriate fractions were collected
  13. customevaporated
  14. customThe residue was recrystallized from ether

Sources & evidence

ORD record
ord-3e890bfee34a4b13884fcd09d55dd7c8
Source dataset
uspto-grants-1993_07
Patent number
US05225412

Reaction notes

Loading…