Methylamine → 7,8-Dimethoxy-3-[3-(methylamino)propyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

HRID 420860Notes

Reaction equation

HRID 420860 reaction equation
[CH3:1][O:2][C:3]1[C:18]([O:19][CH3:20])=[CH:17][C:6]2[CH2:7][C:8](=[O:16])[N:9]([CH2:12][CH2:13][CH:14]=O)[CH2:10][CH2:11][C:5]=2[CH:4]=1.[CH3:21][NH2:22].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[C:18]([O:19][CH3:20])=[CH:17][C:6]2[CH2:7][C:8](=[O:16])[N:9]([CH2:12][CH2:13][CH2:14][NH:22][CH3:21])[CH2:10][CH2:11][C:5]=2[CH:4]=1

Participants

5

Reactant 3

HCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 201441843-(7,8-Dimethoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propionaldehyde

Product 1

HCID 100172197,8-Dimethoxy-3-[3-(methylamino)propyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-oneYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 50 g (0.18 mol) of 3-(7,8-dimethoxy-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)propanal in 625 ml of methanol. Cool the resulting solution to 0° C. and then add 62.5 ml (0.81 mol; 4.5 equivalents) of an aqueous 40% methylamine solution. Stir for one hour at 0° C. and then add 7.5 g (0.2 mol; 1.1 equivalent) of NaBH4. Stir for 30 minutes at 0° C. and then stir for 12 hours at ambient temperature. Evaporate off the methanol. The residue is taken up in aqueous hydrochloric acid solution (1N), and washed with ethyl acetate. The aqueous phase is then adjusted to pH=8 by adding 20% sodium hydroxide solution and extracted with dichloromethane. The organic phase is washed with water, dried over MgSO4, filtered and then evaporated to dryness to obtain 52 g of an oil, which is purified by flash chromatography on 1.5 kg of silica (eluant=dichloromethane/−ethanol/NH4OH:80/20/2). 42 g of the expected product are obtained in the form of a white solid.

Workup

  1. stirringStir for 30 minutes at 0° C.
  2. stirringstir for 12 hours at ambient temperature
  3. customEvaporate off the methanol
  4. washwashed with ethyl acetate
  5. additionby adding 20% sodium hydroxide solution
  6. extractionextracted with dichloromethane
  7. washThe organic phase is washed with water
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-3bc61f152e194724a8376a50b10b9cec
Source dataset
uspto-grants-2012_01
Patent number
US08097720B2

Reaction notes

Loading…