Methyl 4-bromobenzoate → Methyl 4-(4-(((2,4-difluorobenzyl)(2-methyl-3-nitrophenyl)amino)methyl)phenoxy)benzoate

HRID 1370817Notes

Reaction equation

HRID 1370817 reaction equation
[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[C:7]=1[CH3:15].[CH3:29][O:30][C:31](=[O:39])[C:32]1[CH:37]=[CH:36][C:35](Br)=[CH:34][CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:35]2[CH:36]=[CH:37][C:32]([C:31]([O:30][CH3:29])=[O:39])=[CH:33][CH:34]=2)=[CH:19][CH:18]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[C:7]=1[CH3:15]

Participants

7

Reactant 4

HCID 12081Methyl 4-bromobenzoateHCID 62657Potassium Phosphate, TribasicHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 18512160N-(2,4-difluorobenzyl)-N-(4-hydroxybenzyl)-2-methyl-3-nitroaniline

Product 1

HCID 18511913Methyl 4-(4-(((2,4-difluorobenzyl)(2-methyl-3-nitrophenyl)amino)methyl)phenoxy)benzoateYield 92%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The product from Example 33A (0.1520 g, 0.396 mmoles), methyl-4-bromobenzoate (0.1702 g, 0.792 mmoles), K3PO4 (0.1680 g, 0.792 mmoles), Pd(OAc)2 (0.0070 g, 0.032 mmoles), and 2-(di-tert-butylphosphino)biphenyl (0.0140 g, 0.048 mmoles) was treated with toluene (1.16 mL) under a nitrogen atmosphere. The resulting red solution was degassed, stirred for 10 min, and heated to 100° C. overnight. The black solution was diluted with diethyl ether, extracted with sat. NH4Cl and sat. NaCl, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (10:1 hexane:ethyl acetate) on silica gel to provide the title compound (0.1886 g, 92%) as a yellow oil.

Workup

  1. customThe resulting red solution was degassed
  2. additionThe black solution was diluted with diethyl ether
  3. extractionextracted with sat. NH4Cl and sat. NaCl
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (10:1 hexane:ethyl acetate) on silica gel

Sources & evidence

ORD record
ord-69f5b5217bed4a64977b6134fdd8985f
Source dataset
uspto-grants-2003_06
Patent number
US06583180B2

Reaction notes

Loading…