2-Chloroanisole → Hexahydro-3-(3-methoxyphenyl)-2H-azepin-2-one

HRID 848413Notes

Reaction equation

HRID 848413 reaction equation
C[Si](C)(C)[N:3]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]1=[O:10].CC1(C)CCCC(C)(C)N1.C([Li])CCC.Cl[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][CH3:36]>O1CCCC1.CCCCCC.O1CCCC1.CCCCCC.C(OCC)(=O)C.O>[CH3:36][O:35][C:30]1[CH:29]=[C:34]([CH:5]2[CH2:6][CH2:7][CH2:8][CH2:9][NH:3][C:4]2=[O:10])[CH:33]=[CH:32][CH:31]=1

Participants

10

Reactant 4

HCID 130112-ChloroanisoleHCID 130352,2,6,6-TetramethylpiperidineHCID 114239991-Trimethylsilanyl-azepan-2-oneHCID 178418339Butyllithium2×

Product 1

HCID 12875111Hexahydro-3-(3-methoxyphenyl)-2H-azepin-2-oneYield 23.9%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 21883165Tetrahydrofuran hexaneSolvent

Procedure

Hexahydro-1-trimethylsilyl-2H-azepin-2-one (9.2 g) in dry tetrahydrofuran (20 ml) was added dropwise with cooling and stirring under a nitrogen atmosphere to a solution of lithium-2,2,6,6-tetramethylpiperidide (prepared from 2,2,6,6-tetramethylpiperidine (8.48 g) and butyl lithium (0.06 mole) in hexane-tetrahydrofuran (38 ml; 10 ml). A further portion of butyl lithium (0.06 mole) in hexane (38 ml) was then added, followed by o-chloroanisole (8.54 g) keeping the reaction temperature between -10° and 5° C. After allowing to warm to room temperature the reaction was stirred for 1.5 hours then decomposed by the addition of water (100 ml). The solvents were removed under reduced pressure, the resulting product partitioned between toluene and 5 M hydrochloric acid. The toluene extracts were dried (MgSO4), the solvent removed and the product distilled affording 2.7 g b.p. 160°-170° C. at 0.1 mm, which yielded 2.6 g of the crystalline title compound from ethyl acetate.

Workup

  1. temperaturewith cooling
  2. customthe reaction temperature between -10° and 5° C
  3. customThe solvents were removed under reduced pressure
  4. customthe resulting product partitioned between toluene and 5 M hydrochloric acid
  5. dry with materialThe toluene extracts were dried (MgSO4)
  6. customthe solvent removed
  7. distillationthe product distilled
  8. customaffording 2.7 g b.p. 160°-170° C. at 0.1 mm, which

Sources & evidence

ORD record
ord-e272bd83956f4c7fa5957ef88bc086b3
Source dataset
uspto-grants-1981_10
Patent number
US04296029

Reaction notes

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