Diethyl Ether → 1-Methyl-3-(3-oxocyclohex-1-en-1-yl)azepan-2-one

HRID 2049327Notes

Reaction equation

HRID 2049327 reaction equation
Br[CH:2]([CH3:4])[CH3:3].[Mg].[CH:6](NC(C)C)([CH3:8])[CH3:7].[CH3:13][N:14]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][C:15]1=[O:21].CC[O:24]CC>>[CH3:13][N:14]1[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]([C:2]2[CH2:4][CH2:8][CH2:6][C:7](=[O:24])[CH:3]=2)[C:15]1=[O:21]

Participants

6

Reactant 5

HCID 3283Diethyl EtherHCID 63582-BromopropaneHCID 7912DiisopropylamineHCID 17369N-Methylcaprolactam2×HCID 5462224Magnesium

Product 1

HCID 119705831-Methyl-3-(3-oxocyclohex-1-en-1-yl)azepan-2-one

Procedure

2-Bromopropane (12.3 g) was added to suspension of magnesium (2.43 g) in ether (50 ml) at such a rate to maintain gentle reflux and the mixture was stirred 30 minutes after addition was complete. Diisopropylamine (14 ml) was then added dropwise and the mixture stirred until the Gilman test showed negative (about 1 hour). N-methylcaprolactam (12.7 g) was added dropwise (exothermic). After addition of the N-methylcaprolactam, stirring became difficult due to separation of a sticky solid, which however redissolved on addition of THF (50 ml). After the addition was complete the reaction mixture was stirred for 30 minutes then treated dropwise with 3-isopropoxy-2-cyclohexenone (16.4 g) (exothermic) and stirred overnight. The reaction mixture was poured onto 2 N aq HCl (250 ml) and stirred for 30 minutes. Dichloromethane (300 ml) was added and the layers separated. The aqueous layer was extracted with dichloromethane (2×300 ml) and the combined organic phases dried (MgSO4). Removal of the solvents under reduced pressure followed by recrystallisation of the residue from ethyl acetate gave the title compound (13.2 g) identical with the product of Example 3.

Workup

  1. temperatureto maintain gentle
  2. temperaturereflux
  3. additionafter addition
  4. stirringthe mixture stirred until the Gilman test
  5. custom(about 1 hour)
  6. stirringstirring
  7. custombecame difficult due to separation of a sticky solid, which
  8. dissolutionhowever redissolved on addition of THF (50 ml)
  9. additionAfter the addition
  10. stirringwas stirred for 30 minutes
  11. additionthen treated dropwise with 3-isopropoxy-2-cyclohexenone (16.4 g) (exothermic)
  12. stirringstirred overnight
  13. additionThe reaction mixture was poured onto 2 N aq HCl (250 ml)
  14. stirringstirred for 30 minutes
  15. additionDichloromethane (300 ml) was added
  16. customthe layers separated
  17. extractionThe aqueous layer was extracted with dichloromethane (2×300 ml)
  18. dry with materialthe combined organic phases dried (MgSO4)
  19. customRemoval of the solvents under reduced pressure
  20. customfollowed by recrystallisation of the residue from ethyl acetate

Sources & evidence

ORD record
ord-e52028121a594a59b90c0767aefd3946
Source dataset
uspto-grants-1980_04
Patent number
US04197241

Reaction notes

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