Monobenzone → 4-(4-(benzyloxy)phenoxy)-N-methylpicolinamide

HRID 491663Notes

Reaction equation

HRID 491663 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:18][NH:19][C:20]([C:22]1[CH:27]=[C:26](OC2C=CC([N+]([O-])=O)=C([N+]([O-])=O)C=2)[CH:25]=[CH:24][N:23]=1)=[O:21]>CN(C=O)C>[CH3:18][NH:19][C:20]([C:22]1[CH:27]=[C:26]([O:17][C:14]2[CH:13]=[CH:12][C:11]([O:10][CH2:3][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)=[CH:16][CH:15]=2)[CH:25]=[CH:24][N:23]=1)=[O:21]

Participants

5

Reactant 3

HCID 7638MonobenzoneHCID 24758Sodium hydrideHCID 17756075HCID 17756075, compound

Product 1

HCID 177564984-(4-(benzyloxy)phenoxy)-N-methylpicolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred RT slurry of NaH (2.24 g of 60% oil dispersion, 55.9 mmol) in 40 mL DMF was added 4-benzyloxyphenol (11.2 g, 55.9 mmol). The mixture was stirred for 10 min before adding 4-chloro-pyridine-2-carboxylic acid methylamide (Example 2 Step A, 3.18 g, 18.6 mmol). The reaction was stirred at RT for 5 min, then at 75° C. for 2 h, and finally at 85° C. for 6 h. The reaction was cooled to RT, quenched with saturated aqueous NaHCO3, then diluted with Et2O and 6 N NaOH. The layers were separated, and the organic layer was washed twice with 6 N NaOH, once with brine, dried over Na2SO4, filtered, and concentrated in vacuo, to yield the title compound as a light salmon-colored solid. MS (MH+)=335.1; MW Calc'd 334.38 for C20H18N2O3.

Workup

  1. stirringThe reaction was stirred at RT for 5 min
  2. waitat 75° C. for 2 h
  3. waitfinally at 85° C. for 6 h
  4. customquenched with saturated aqueous NaHCO3
  5. additiondiluted with Et2O and 6 N NaOH
  6. customThe layers were separated
  7. washthe organic layer was washed twice with 6 N NaOH, once with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e824c6d5ab634929902c3a09ba95f7bb
Source dataset
uspto-grants-2009_05
Patent number
US07531553B2

Reaction notes

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