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

HRID 848412Notes

Reaction equation

HRID 848412 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[CH2:16]([CH:18]1[CH2:24][CH2:23][CH2:22][CH2:21][N:20]([CH3:25])[C:19]1=[O:26])[CH3:17].Cl[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[O:34][CH3:35]>CCCCCC.O1CCCC1.O>[CH2:16]([C:18]1([C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([O:34][CH3:35])[CH:28]=2)[CH2:24][CH2:23][CH2:22][CH2:21][N:20]([CH3:25])[C:19]1=[O:26])[CH3:17]

Participants

8

Reactant 4

HCID 130112-ChloroanisoleHCID 130352,2,6,6-TetramethylpiperidineHCID 1084053-Ethylhexahydro-1-methyl-2H-azepin-2-oneHCID 178418339Butyllithium2×

Product 1

HCID 27290973-Ethylhexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent2×

Procedure

2,2,6,6-tetramethylpiperidine (8.48 g) was added dropwise with cooling and stirring under nitrogen to a solution of butyl lithium (0.05 mole) in hexane (31.25 ml) and tetrahydrofuran (15 ml). 3-Ethylhexahydro-1-methyl-2H-azepin-2-one (7.75 g) in dry tetrahydrofuran (20 ml) was added. On completion of this addition a further portion of butyl lithium (0.06 mole) in hexane (37.5 ml) was added with cooling. After ten minutes o-chloroanisole (8.54 g) was added dropwise in tetrahydrofuran (20 ml). The reaction was then stirred at ambient temperature for c.a. 20 hours. The reaction mixture was poured into water, and the tetrahydrofuran removed under reduced pressure. After acidifying with 5 M hydrochloric acid the mixture was extracted with toluene. Toluene extracts were washed with water, dried (MgSO4) and after removal of the solvent the product distilled affording 2.37 g, b.p. 150°-170° C. at 0.6 mm. Corrected by purity by g.l.c. assay, the yield of the title compound was 15.8%.

Workup

  1. temperaturewith cooling
  2. additionwas added
  3. temperaturewith cooling
  4. custom20 hours
  5. customthe tetrahydrofuran removed under reduced pressure
  6. extractionwas extracted with toluene
  7. washToluene extracts were washed with water
  8. dry with materialdried (MgSO4)
  9. customafter removal of the solvent the product
  10. distillationdistilled
  11. customaffording 2.37 g, b.p. 150°-170° C. at 0.6 mm

Sources & evidence

ORD record
ord-b4fe3d5fa45245a9ba6d5b2e3713cd90
Source dataset
uspto-grants-1981_10
Patent number
US04296029

Reaction notes

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