2-Chloroanisole → hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one

HRID 848410Notes

Reaction equation

HRID 848410 reaction equation
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[CH3:16][N:17]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][C:18]1=[O:24].Cl[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH3:33]>CCCCCC.C1COCC1>[CH3:33][O:32][C:27]1[CH:26]=[C:31]([CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][N:17]([CH3:16])[C:18]2=[O:24])[CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 130112-Chloroanisole2×HCID 130352,2,6,6-TetramethylpiperidineHCID 17369N-MethylcaprolactamHCID 178418339Butyllithium3×

Product 1

HCID 2727906hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent3×

Procedure

A solution of butyl lithium (0.05 mole) in hexane (34.4 ml), was treated with 2,2,6,6-tetramethylpiperidine (9.3 ml) followed by dry THF (100 ml) under an inert atmosphere at 0° C. The mixture was treated with N-methylcaprolactam (6.9 ml, 55 mM) and stirred for 30 minutes. A solution of butyl lithium (0.05 mole) in hexane (34.4 ml) was added, the reaction mixture stirred 15 minutes then treated with o-chloroanisole (3.1 ml). After 30 minutes a solution of butyl lithium (0.05 moles) in hexane (31.25 ml) was added, the mixture stirred for 15 minutes and treated with o-chloroanisole (3.1 ml). After a further 30 minutes, the reaction was quenched with water (100 ml) and the solvents removed under reduced pressure. The residue was partitioned between 5 N HCl (100 ml) and toluene (250 ml). The organic phase was washed with brine, dried and the solvents removed under reduced pressure.

Workup

  1. stirringthe reaction mixture stirred 15 minutes
  2. stirringthe mixture stirred for 15 minutes
  3. waitAfter a further 30 minutes
  4. customthe reaction was quenched with water (100 ml)
  5. customthe solvents removed under reduced pressure
  6. customThe residue was partitioned between 5 N HCl (100 ml) and toluene (250 ml)
  7. washThe organic phase was washed with brine
  8. customdried
  9. customthe solvents removed under reduced pressure

Sources & evidence

ORD record
ord-bea295edcbe94a7193f2239d34c0963b
Source dataset
uspto-grants-1981_10
Patent number
US04296029

Reaction notes

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