Benzenemethanamine, 3,4-dichloro- → 8-[(3,4-Dichlorophenyl)methyl]-8-azabicyclo[3.2.1]octan-3-one

HRID 1070519Notes

Reaction equation

HRID 1070519 reaction equation
CO[CH:3]1[CH2:7][CH2:6][CH:5](OC)[O:4]1.[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[Cl:19])[CH2:14][NH2:15].[OH-].[Na+].[CH3:22][C:23]([CH3:25])=O.C(O)=O.C(O)=O>Cl.P([O-])([O-])([O-])=O>[Cl:10][C:11]1[CH:12]=[C:13]([CH2:14][N:15]2[CH:6]3[CH2:5][CH2:25][CH:23]2[CH2:22][C:3](=[O:4])[CH2:7]3)[CH:16]=[CH:17][C:18]=1[Cl:19]

Participants

7

Reactant 4

HCID 1608Benzenemethanamine, 3,4-dichloro-HCID 14798Sodium HydroxideHCID 790982,5-DimethoxytetrahydrofuranHCID 53400708Acetone dicarboxylic acid

Product 1

HCID 223961488-[(3,4-Dichlorophenyl)methyl]-8-azabicyclo[3.2.1]octan-3-one

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 1061PhosphateSolvent2×

Procedure

2,5-Dimethoxytetrahydrofuran (4.92 g) was stirred in hydrochloric acid (1M, 25 ml) for 1 hour. 3,4-Dichlorobenzylamine (5 ml) was added to hydrochloric acid (1M, 15 ml) and the resulting suspension was added to the first solution. Phosphate buffer solution (pH 5.5, 250 ml) was added followed by sodium hydroxide (1.6 g). A solution of acetone dicarboxylic acid (4.77 g) in phosphate buffer solution (pH 5.5, 90 ml) was added to the mixture and the solution was stirred. A yellow solid formed and the mixture was left to stand for 64 h. The aqueous supernatant was decanted and hydrochloric acid (2.5M) was added to the solid along with ethyl acetate. The layers were separated and the aqueous phase was extracted twice with dichloromethane containing a little methanol. The organic layers were combined and evaporated to give a crude oil (ca 7 g). A portion of the product (ca 2.5 g) was purified by chromatography eluting with dichloromethane:methanol (19:1) to give the subtitle compound (1.62 g) as a yellow oil.

Workup

  1. additionthe resulting suspension was added to the first solution
  2. customA yellow solid formed
  3. waitthe mixture was left
  4. customThe aqueous supernatant was decanted
  5. additionhydrochloric acid (2.5M) was added to the solid along with ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted twice with dichloromethane containing a little methanol
  8. customevaporated
  9. customto give a crude oil (ca 7 g)
  10. customA portion of the product (ca 2.5 g) was purified by chromatography
  11. washeluting with dichloromethane:methanol (19:1)

Sources & evidence

ORD record
ord-738d469ab65e4dd4b5e696edefd11b85
Source dataset
uspto-grants-2005_06
Patent number
US06903085B1

Reaction notes

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