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

HRID 848415Notes

Reaction equation

HRID 848415 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[CH3:19][N:20]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][C:21]1=[O:27].Cl[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][CH3:36]>O1CCCC1.O>[CH3:36][O:35][C:30]1[CH:29]=[C:34]([CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][N:20]([CH3:19])[C:21]2=[O:27])[CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8058HexaneHCID 130112-ChloroanisoleHCID 17369N-MethylcaprolactamHCID 178418339Butyllithium

Product 1

HCID 2727906hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-oneYield 23.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Diisopropylamine (152 g) in tetrahydrofuran (150 ml) was added over 30 minutes to 15% butyl lithium in hexane (641 g, 1.50 mole) under nitrogen at 20°-25° C. with cooling and the mixture stirred 30 minutes at room temperature. N-methylcaprolactam (63.6 g) in tetrahydrofuran (60 ml) was added over 5 minutes below 25° C. with cooling, the mixture was stirred for one hour at room temperature and then o-chloroanisole (71.3 g) was added over 20 minutes keeping the temperature below 30° C. The reaction mixture was stirred for two hours, water (2. l.) was added, the product was extracted into ethyl acetate (2×1 l.), the extracts were combined, washed with 2 N hydrochloric acid (1. l.) and water (500 ml) and evaporated under reduced pressure to give 27.1 g oil.

Workup

  1. temperaturewith cooling
  2. temperaturewith cooling
  3. stirringthe mixture was stirred for one hour at room temperature
  4. customthe temperature below 30° C
  5. stirringThe reaction mixture was stirred for two hours
  6. extractionthe product was extracted into ethyl acetate (2×1 l.)
  7. washwashed with 2 N hydrochloric acid (1. l.) and water (500 ml)
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8db5bc67f79b44f0b3d6da3995574607
Source dataset
uspto-grants-1981_10
Patent number
US04296029

Reaction notes

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