Potassium Carbonate → HCID 15520898, compound

HRID 565141Notes

Reaction equation

HRID 565141 reaction equation
[C:1]([CH2:8][N:9]1[C:15]2[CH:16]=[CH:17][C:18](O)=[CH:19][C:14]=2[C:13](=[O:21])[N:12]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:11][C:10]1=[O:29])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([CH2:8][N:9]1[C:15]2[CH:16]=[CH:17][C:18]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)=[CH:19][C:14]=2[C:13](=[O:21])[N:12]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:11][C:10]1=[O:29])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 869964-(Bromomethyl)benzonitrileHCID 15520897HCID 15520897, compound

Product 1

HCID 15520898HCID 15520898, compoundYield 85.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

1-(Carbo-t-butoxymethyl)-4-(2-carboethoxyethyl)-7-hydroxy-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (19.5 g, 48 mmol), α-bromo-p-tolunitrile (11.3 g, 58 mmol), and potassium carbonate (9.0 g, 65 mmol) were combined in a round bottom flask. Anhydrous DMF (300 mL) was added and the reaction mixture was stirred at 40° C. for 4 days. The reaction mixture was filtered and the filtrate was concentrated in vacuo on a rotary evaporator. The residue was partitioned between ethyl acetate (500 mL) and water (100 mL). The organics were washed with saturated NaCl (50 mL) and dried over Na2SO4. The volatiles were removed in vacuo on a rotary evaporator and the residue was chromatographed on silica gel, eluting the column with 5:6 ethyl acetate/hexanes. Fractions containing pure product (Rf=0.17, 5:6 ethyl acetate/hexanes) were combined and the solvents removed in vacuo on a rotary evaporator to yield 1-(carbo-t-butoxymethyl)-4-(2-carboethoxyethyl)-7-[(4-cyanophenyl)methyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (20.7 g, 83% yield).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo on a rotary evaporator
  3. customThe residue was partitioned between ethyl acetate (500 mL) and water (100 mL)
  4. washThe organics were washed with saturated NaCl (50 mL)
  5. dry with materialdried over Na2SO4
  6. customThe volatiles were removed in vacuo on a rotary evaporator
  7. customthe residue was chromatographed on silica gel
  8. washeluting the column with 5:6 ethyl acetate/hexanes
  9. additionFractions containing pure product (Rf=0.17, 5:6 ethyl acetate/hexanes)
  10. customthe solvents removed in vacuo on a rotary evaporator

Sources & evidence

ORD record
ord-35f64606562f44778aab3ddaae4551b1
Source dataset
uspto-grants-2001_01
Patent number
US06171578B2

Reaction notes

Loading…