Benzenesulfonic Acid → HCID 86641481, compound

HRID 1042759Notes

Reaction equation

HRID 1042759 reaction equation
Cl.[Br:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][O:19][CH3:20].[OH-].[K+].[CH:23]1[CH:28]=[CH:27][C:26]([S:29]([O:32][CH2:33][CH2:34][C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[O:41][CH2:40][CH2:39][C:38]3=[O:45])(=[O:31])=[O:30])=[CH:25][CH:24]=1.P([O-])([O-])(O)=O.[K+].[K+].CN1CCCCC1=O.C1(S(O)(=O)=O)C=CC=CC=1>CC(C)=O.C(OCCCC)(=O)C.C1(C)C=CC=CC=1.O1CCCC1.O>[C:26]1([S:29]([OH:32])(=[O:31])=[O:30])[CH:27]=[CH:28][CH:23]=[CH:24][CH:25]=1.[Br:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][CH:8]2[CH2:9][CH2:10][N:11]([CH2:33][CH2:34][C:35]3[CH:36]=[C:37]4[C:42](=[CH:43][CH:44]=3)[O:41][CH2:40][CH2:39][C:38]4=[O:45])[CH2:12][CH2:13]2)=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][O:19][CH3:20]

Participants

12

Reactant 6

HCID 7371Benzenesulfonic AcidHCID 13603N-Methyl-2-piperidoneHCID 14797Potassium HydroxideHCID 24450Potassium Phosphate, DibasicHCID 67000209HCID 67000209, compoundHCID 86641482HCID 86641482, compound

Product 1

HCID 86641481HCID 86641481, compoundYield 89%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolventHCID 31272Butyl AcetateSolvent2×

Conditions

Temperature
115 °C

Procedure

4-[4-Bromo-3-(2-methoxyethoxy)benzyl]piperidine hydrochloride (2.0 g, 5.48 mmol) was added to an aqueous potassium hydroxide solution (prepared from potassium hydroxide [0.43 g, 6.58 mmol] and water [10 ml]), followed by extraction with toluene (10 ml×2). All the organic layers were combined, and the solvent was distilled off under reduced pressure. 6-(2-p-Benzenesulfonyloxyethyl)-2,3-dihydro-4H-chromen-4-one (1.91 g, 5.76 mmol), dipotassium hydrogen phosphate (2.87 g, 16.5 mmol), N-methyl-2-piperidone (0.6 ml), and toluene (20 ml) were added to the concentrated residue, and the mixture was stirred at 110 to 120° C. for 6 hours. After cooling to 40 to 50° C., water (20 ml), tetrahydrofuran (10 ml), and toluene (10 ml) were added thereto. The organic layer was washed with water (10 ml). The solvent was distilled off under reduced pressure to obtain a concentrated residue. The obtained concentrated residue was dissolved in acetone (6.0 ml) without further purification, and a solution of benzenesulfonic acid (0.93 g, 5.76 mmol) in acetone (4.0 ml) was added dropwise thereto at 50 to 60° C. The mixture was stirred at 50 to 60° C. for 30 minutes. Then, n-butyl acetate (20.0 ml) was added dropwise thereto, and the mixture was further stirred for 1 hour. After cooling to room temperature, n-butyl acetate (10 ml) was added dropwise thereto, and the mixture was stirred for 3.5 hours in an ice bath. The precipitate was collected by filtration, washed with cold acetone (4.0 ml×2), and dried under reduced pressure to obtain the title compound (3.21 g, 89%).

Workup

  1. extractionfollowed by extraction with toluene (10 ml×2)
  2. distillationthe solvent was distilled off under reduced pressure
  3. temperatureAfter cooling to 40 to 50° C.
  4. washThe organic layer was washed with water (10 ml)
  5. distillationThe solvent was distilled off under reduced pressure
  6. customto obtain a concentrated residue
  7. customat 50 to 60° C
  8. stirringThe mixture was stirred at 50 to 60° C. for 30 minutes
  9. stirringthe mixture was further stirred for 1 hour
  10. temperatureAfter cooling to room temperature
  11. stirringthe mixture was stirred for 3.5 hours in an ice bath
  12. filtrationThe precipitate was collected by filtration
  13. washwashed with cold acetone (4.0 ml×2)
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-1d75361176ef43e4941cd2ba3f80ba17
Source dataset
uspto-grants-2013_10
Patent number
US08557998B2

Reaction notes

Loading…