Ethyl Acetate → 2-Benzyloxy-4-(2-chloro-4-methoxy-phenyl)-3-nitro-pyridine

HRID 1831517Notes

Reaction equation

HRID 1831517 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.C([O-])([O-])=O.[Na+].[Na+].[Cl:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=1B(O)O.CCOC(C)=O>C(O)C.C1(C)C=CC=CC=1.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.O>[CH2:1]([O:8][C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[C:13]([C:27]2[CH:28]=[CH:29][C:30]([O:32][CH3:33])=[CH:31][C:26]=2[Cl:25])[CH:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27733302-Chloro-4-methoxybenzeneboronic acidHCID 220520652-(Benzyloxy)-4-chloro-3-nitropyridine

Product 1

HCID 220520422-Benzyloxy-4-(2-chloro-4-methoxy-phenyl)-3-nitro-pyridineYield 36%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 2-benzyloxy-4-chloro-3-nitro-pyridine (Wilde, et al. WO 99/01454, which is incorporated herein by reference) (3.0 g, 11.3 mmol) in ethanol (10 mL) and toluene (40 mL), was added Na2CO3 (14.17 mL, 2 M), 2-chloro-4-methoxyphenylboronic acid (3.17 g, 17.0 mmol), and Pd(PPh3)2Cl2 (0.48 g, 0.68 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. Purification using flash chromatography (10% EtOAc-Hexane) gave 1.51 g (36%) of 2-benzyloxy-4-(2-chloro-4-methoxy-phenyl)-3-nitro-pyridine as a viscous oil: MS (AP) m/z 370.8 [(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
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification

Sources & evidence

ORD record
ord-275800b5b3844a6ea97e4c7887d7345a
Source dataset
uspto-grants-2006_06
Patent number
US07067658B2

Reaction notes

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