Water → 2-Benzyloxy-4-(2-chloro-4-difluoromethoxy-phenyl)-3-nitro-pyridine

HRID 1831548Notes

Reaction equation

HRID 1831548 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[C:13](Cl)[CH:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:25]=[C:24]([O:26][CH:27]([F:29])[F:28])[CH:23]=[CH:22][C:21]=1B(O)O.CCOC(C)=O.O>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[C:13]([C:21]2[CH:22]=[CH:23][C:24]([O:26][CH:27]([F:28])[F:29])=[CH:25][C:20]=2[Cl:19])[CH:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 22052056(2-Chloro-4-(difluoromethoxy)phenyl)boronic acidHCID 220520652-(Benzyloxy)-4-chloro-3-nitropyridine

Product 1

HCID 220520472-Benzyloxy-4-(2-chloro-4-difluoromethoxy-phenyl)-3-nitro-pyridineYield 68%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

To a solution of 2-benzyloxy-4-chloro-3-nitro-pyridine (Wilde, et al. WO 99/01454, which is incorporated herein by reference) (6.59 g, 24.9 mmol) in DME/H2O, was added 2-chloro-4-difluoromethoxy-phenylboronic acid (Wilde, et al. WO 99/01454) (5.54 g, 24.9 mmol), Ba(OH)2 8H2O (7.86 g, 24.9 mmol), and Pd(PPh3)2Cl2 (1.01 g, 1.45 mmol) and the mixture was heated at reflux for 5 h. The reaction was cooled and poured into EtOAc and H2O (500 mL). The EtOAc layer was washed with H2O, brine, dried Na2SO4, filtered and concentrated in vacuo to give 6.9 g (68%) of 2-benzyloxy-4-(2-chloro-4-difluoromethoxy-phenyl)-3-nitro-pyridine as a viscous oil; MS(AP) m/z 408.9 [(M+H)+, 100].

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 5 h
  3. temperatureThe reaction was cooled
  4. washThe EtOAc layer was washed with H2O, brine, dried Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fd79df0ca8cf4f239cb05b304b695031
Source dataset
uspto-grants-2006_06
Patent number
US07067658B2

Reaction notes

Loading…