2-Chloroanisole → 1-Benzyl-3-(3-methoxyphenyl)-2-azepanone

HRID 848414Notes

Reaction equation

HRID 848414 reaction equation
[CH2:1]([N:8]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)CCCC(C)(C)N1.C([Li])CCC.Cl[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[O:38][CH3:39]>O1CCCC1.CCCCCC.O>[CH2:1]([N:8]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]([C:37]2[CH:36]=[CH:35][CH:34]=[C:33]([O:38][CH3:39])[CH:32]=2)[C:9]1=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 130112-ChloroanisoleHCID 130352,2,6,6-TetramethylpiperidineHCID 14910681-Benzylazepan-2-oneHCID 178418339Butyllithium2×

Product 1

HCID 205653371-Benzyl-3-(3-methoxyphenyl)-2-azepanone

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1-Benzylhexahydro-2H-azepin-2-one (10.2 g) in tetrahydrofuran (100 ml) was added dropwise to a stirred, cooled solution of lithium-2,2,6,6-tetramethylpiperidide [prepared by the addition of 2,2,6,6-tetramethylpiperidine (8.5 g) to butyl lithium (0.05 mole) in hexane (32 ml)] under nitrogen. When the addition was completed a further portion of butyl lithium (0.05 mole) in hexane (32 ml) was added. The solution was cooled to 0° C. and o-chloroanisole (6.2 ml) added dropwise. After stirring at room temperature for four hours the reaction was decomposed with water and the solvents removed under reduced pressure. The resulting oil was partitioned between 5 M hydrochloric acid and toluene. After drying (MgSO4) the toluene was removed to leave an oil which was distilled affording 5.02 g b.p. 180°-220° C. at 0.2 mm. The oil was crystallised from methanol, affording 3.15 g m.p. 120°-122° C.

Workup

  1. additionWhen the addition
  2. additionwas added
  3. customthe solvents removed under reduced pressure
  4. customThe resulting oil was partitioned between 5 M hydrochloric acid and toluene
  5. dry with materialAfter drying (MgSO4) the toluene
  6. customwas removed
  7. customto leave an oil which
  8. distillationwas distilled
  9. customaffording 5.02 g b.p. 180°-220° C. at 0.2 mm
  10. customThe oil was crystallised from methanol
  11. customaffording 3.15 g m.p. 120°-122° C.

Sources & evidence

ORD record
ord-1431711e01d04526923d1330c5bbef03
Source dataset
uspto-grants-1981_10
Patent number
US04296029

Reaction notes

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