N-methyl-2-pyrrolidone → Methyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate

HRID 13994

Reaction equation

HRID 13994 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]([N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])=[O:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[Si](C)(C)N[Si](C)(C)C.C(N(C(C)C)CC)(C)C.C[N:69]1[C:73](=[O:74])CCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:69][C:73]([C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]([N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])=[O:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])=[O:74]

Participants

7

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 13838HexamethyldisilazaneHCID 812191,3-Bis(diphenylphosphino)propaneHCID 81531DiisopropylethylamineHCID 21939662Methyl 3-bromo-5-(dipropylcarbamoyl)benzoate

Product 1

HCID 22593626Methyl 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoate

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

To a mixture of methyl 3-bromo-5-[(dipropylamino)carbonyl]benzoate (XXI, PREPARATION 3, 0.5 g, 1.47 mmol) in dry N-methyl pyrrolidinone under a carbon monoxide atmosphere is added palladium (II) acetate (0.017 g, 0.074 mmol), 1,3-bis(diphenylphosphino)propane (0.045 g, 0.11 mmol), hexamethyldisilazane (1.0 mL, 4.7 mmol), and diisopropylethylamine (0.38 g, 2.94 mmol). The mixture is heated at 100 degrees C. for 24 hours. The mixture is cooled to 20-25 degrees C. and partitioned between water and ethyl acetate. The layers are separated and the aqueous phase is back-washed with ethyl acetate. The organic phases are combined and washed three times with saline, dried over anhydrous magnesium sulfate, filtered and concentrated. Column chromatography (silica gel, 75 mL; methanol/methylene chloride, 2.5/97.5) gives the title compound, NMR (CDCl3) delta 0.77, 1.02, 1.57, 1.71, 3.17, 3.49, 3.98, 5.78, 6.34, 8.07, 8.20 and 8.48.

Workup

  1. temperatureThe mixture is cooled to 20-25 degrees C
  2. customand partitioned between water and ethyl acetate
  3. customThe layers are separated
  4. washthe aqueous phase is back-washed with ethyl acetate
  5. washwashed three times with saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-29f5d0eb949941ada3d0a5cf90557324
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

Loading…