Formaldehyde → 1,3-dihydro-3-hydroxymethyl-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one

HRID 1729097Notes

Reaction equation

HRID 1729097 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:5][CH2:4][C:3]1=[O:19].[CH2:20]=[O:21].[OH-].[Na+]>C(OCC)(=O)C>[OH:21][CH2:20][CH:4]1[N:5]=[C:6]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:2]([CH3:1])[C:3]1=[O:19]

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 14798Sodium Hydroxide2×HCID 6138431-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one

Product 1

HCID 190135541,3-dihydro-3-hydroxymethyl-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-oneYield 15%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A reaction mixture of 1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (J. Org. Chem. 52, 3232, (1987)) (12.6 g, 50 mmol), formaline-solution (37% in water, 75 mL) and sodium hydroxide (4.4 g, 110 mmol) was heated to reflux for 4.5 hours. Then additional formaline solution (35 mL) and sodium hydroxide (2.2 g) was added and the reaction mixture was heated for 4 hours. The cooled suspension was diluted with ethyl acetate, the organic layer separated, washed with water and dried over Na2SO4. The organicsolution was evaporated in vacuum and the residue flash-chromatographed on silica gel using toluene/ethanol (3.5%) as eluant to give 1,3-dihydro-3-hydroxymethyl-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (2.15 g, 15%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4.5 hours
  3. temperaturethe reaction mixture was heated for 4 hours
  4. customthe organic layer separated
  5. washwashed with water
  6. dry with materialdried over Na2SO4
  7. customThe organicsolution was evaporated in vacuum
  8. customthe residue flash-chromatographed on silica gel

Sources & evidence

ORD record
ord-7653c6c38adb466e818d516604b514e9
Source dataset
uspto-grants-1994_07
Patent number
US05331006

Reaction notes

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