3-Bromo-N-methoxy-N-methylbenzamide → N-{2-[(3-bromophenyl)carbonyl]-4,5-dimethoxyphenyl}-2,2-dimethylpropanamide

HRID 1191328Notes

Reaction equation

HRID 1191328 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15].[Li]CCCC.[Br:24][C:25]1[CH:26]=[C:27]([CH:34]=[CH:35][CH:36]=1)[C:28](N(OC)C)=[O:29]>C1COCC1>[Br:24][C:25]1[CH:26]=[C:27]([C:28]([C:2]2[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=2[NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[O:29])[CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 121628753-Bromo-N-methoxy-N-methylbenzamideHCID 66849105N-(2-bromo-4,5-dimethoxyphenyl)pivalamideHCID 178418339Butyllithium

Product 1

HCID 66849003N-{2-[(3-bromophenyl)carbonyl]-4,5-dimethoxyphenyl}-2,2-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A flamed dried 500 mL three-necked flask was charged N-(2-bromo-4,5-dimethoxyphenyl)-2,2-dimethylpropanamide (30 g, 95 mmol) and dry THF (200 mL) under N2. n-BuLi (114 mL, 2.5 mol/L, 285 mmol) was added dropwise at −78° C. After the mixture was stirred at −78° C. for 1 hour, 3-bromo-N-methoxy-N-methylbenzamide (23.2 g, 94.9 mmol) in dry THF (30 mL) was added dropwise slowly at −78° C. The resulting mixture was stirred at −78° C. for 3 hours, then quenched with saturated NH4Cl (100 mL). The mixture was exacted with EtOAc (100 mL×3). The combined organic phases were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column (30:1 hexanes/ethyl acetate) to afford a N-{2-[(3-bromophenyl)carbonyl]-4,5-dimethoxyphenyl}-2,2-dimethylpropanamide as a yellow solid. MS (M+H)=420 and 422.

Workup

  1. customA flamed dried 500 mL three-necked flask
  2. stirringThe resulting mixture was stirred at −78° C. for 3 hours
  3. customquenched with saturated NH4Cl (100 mL)
  4. dry with materialThe combined organic phases were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column (30:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d768d10a66cb4d1aaeab7bc86525be03
Source dataset
uspto-grants-2014_03
Patent number
US08680116B2

Reaction notes

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