Methyl{4-chloro-2-[cyano(2-methoxyphenyl)methyl]phenyl}acetate → 7-Chloro-5-(2-methoxyphenyl)-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

HRID 1444827Notes

Reaction equation

HRID 1444827 reaction equation
C[O:2][C:3](=O)[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:6]=1[CH:12]([C:21]#[N:22])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20]>C(O)C.[Ni]>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[CH2:4][C:3](=[O:2])[NH:22][CH2:21][CH:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])[C:6]=2[CH:7]=1

Participants

4

Reactant 1

HCID 59025540Methyl{4-chloro-2-[cyano(2-methoxyphenyl)methyl]phenyl}acetate

Product 1

HCID 590254937-Chloro-5-(2-methoxyphenyl)-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

201 mg of the compound from Example 20A (0.61 mol) are dissolved in 30 ml of ethanol, introduced into a hydrogenation apparatus and mixed with anhydrous Raney nickel. The catalyst has previously been obtained by washing 1.0 ml of a 50% strength aqueous Raney nickel suspension with ethanol several times. Hydrogenation is carried out under atmospheric pressure and at room temperature for 2.5 h. The catalyst is then filtered off under an argon atmosphere and washed three times with ethanol, and the combined filtrates are concentrated. The residue is dissolved in 30 ml of toluene and heated under reflux for 5 h. The solvent is removed in a rotary evaporator, and the residue is purified by preparative HPLC (eluent: acetonitrile/water, gradient 20:80→95:5). 55 mg (30% of theory) of the title compound are obtained.

Workup

  1. additionintroduced into a hydrogenation apparatus
  2. customThe catalyst has previously been obtained
  3. washby washing 1.0 ml of a 50% strength aqueous Raney nickel suspension with ethanol several times
  4. filtrationThe catalyst is then filtered off under an argon atmosphere
  5. washwashed three times with ethanol
  6. concentrationthe combined filtrates are concentrated
  7. dissolutionThe residue is dissolved in 30 ml of toluene
  8. temperatureheated
  9. temperatureunder reflux for 5 h
  10. customThe solvent is removed in a rotary evaporator
  11. customthe residue is purified by preparative HPLC (eluent: acetonitrile/water, gradient 20:80→95:5)

Sources & evidence

ORD record
ord-caf3cfecd5e54713b28b2dc0f629b66e
Source dataset
uspto-grants-2010_02
Patent number
US07662956B2

Reaction notes

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