1,2-Dichloroethane → HCID 22990195, compound

HRID 1169429Notes

Reaction equation

HRID 1169429 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH2:10][CH2:11][O:12][C:13]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=4)=[CH:16][C:14]=3[CH:15]=2)[CH2:4][CH2:3]1.[O:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O.[Cl:50]CCCl>>[ClH:50].[ClH:50].[CH3:26][C:23]1[CH:24]=[CH:25][C:20]([C:17]2[CH:18]=[CH:19][C:13]3[O:12][CH2:11][CH2:10][C:9]([CH2:8][N:5]4[CH2:4][CH2:3][CH:2]([N:1]([CH3:34])[CH:30]5[CH2:31][CH2:32][O:27][CH2:28][CH2:29]5)[CH2:7][CH2:6]4)=[CH:15][C:14]=3[CH:16]=2)=[CH:21][CH:22]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 712FormaldehydeHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydride2×HCID 22990220HCID 22990220, compound

Product 1

HCID 22990195HCID 22990195, compound

Procedure

To 4-amino-1-(7-(4-methylphenyl)-2,3-dihydro-1-benzooxepin-4-yl)methylpiperidine (0.3 g) and tetrahydro-4H-pyran-4-one (0.09 g) dissolved in 1,2-dichloroethane (10 ml) was added under ice cooling sodium triacetoxyborohydride (0.26 g). The resulting mixture was stirred at room temperature overnight under a nitrogen atmosphere. Thereto was added a 37% aqueous solution of formaldehyde (0.1 ml) and was then added under ice cooling sodium triacetoxyborohydride (0.3 g), and the resulting mixture was stirred at room temperature overnight under a nitrogen atmosphere. The reaction mixture was evaporated to remove the solvent, was neutralized with a 1 N aqueous solution of sodium hydroxide and was then extracted with ethyl acetate. The organic layer was washed with water and an aqueous saturated solution of sodium chloride and was then dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was subjected to purification using a silica gel column (methanol/triethylamine/ethyl acetate). The purified material dissolved in ethyl acetate was mixed with 4 N hydrochloric acid/ethyl acetate (0.4 ml) and hexane to collect the precipitated powder by filtration. The powder was washed with hexane to obtain 1-(7-(4-methylphenyl)-2,3-dihydro-1-benzooxepin-4-yl)methyl-4-(N-methyl-N-(tetrahydropyran-4-yl)amino)piperidine dihydrochloride (compound 81) (0.21 g) as a colorless amorphous substance.

Workup

  1. additionwas added under ice
  2. additionwas then added under ice
  3. stirringthe resulting mixture was stirred at room temperature overnight under a nitrogen atmosphere
  4. customThe reaction mixture was evaporated
  5. customto remove the solvent
  6. extractionwas then extracted with ethyl acetate
  7. washThe organic layer was washed with water
  8. dry with materialan aqueous saturated solution of sodium chloride and was then dried with anhydrous magnesium sulfate
  9. customthe solvent was evaporated
  10. customThe residue was subjected to purification
  11. dissolutionThe purified material dissolved in ethyl acetate
  12. additionwas mixed with 4 N hydrochloric acid/ethyl acetate (0.4 ml) and hexane
  13. customto collect the precipitated powder
  14. filtrationby filtration
  15. washThe powder was washed with hexane

Sources & evidence

ORD record
ord-983faca772cc42039edd63563f4054e5
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

Loading…