Sodium Carbonate → 5-(3-chlorophenyl)-N-methoxy-N-methylbenzamide

HRID 2099203Notes

Reaction equation

HRID 2099203 reaction equation
N[C:2]1[CH:13]=[CH:12][C:11](Br)=[CH:10][C:3]=1[C:4]([N:6]([O:8][CH3:9])[CH3:7])=[O:5].[Cl:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:15][C:16]1[CH:21]=[C:20]([C:11]2[CH:12]=[CH:13][CH:2]=[C:3]([CH:10]=2)[C:4]([N:6]([O:8][CH3:9])[CH3:7])=[O:5])[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 159081302-amino-5-bromo-N-methoxy-N-methylbenzamide

Product 1

HCID 220218875-(3-chlorophenyl)-N-methoxy-N-methylbenzamideYield 60.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-amino-5-bromo-N-methoxy-N-methylbenzamide (7.78 g, 30 mmol), 3-chlorophenyl boronic acid (5.63 g, 36 mmol), tetrakis(triphenylphosphine)palladium (0) (1.73 g, 1.5 mmol), and sodium carbonate (7.63 g, 72 mmol) in a mixture of DME and water (150 mL/30 mL) was degassed to remove the oxygen and heated at 85° C. under nitrogen for 3 hours. The reaction mixture was cooled to room temperature and treated with brine (30 mL) and ethyl acetate (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with brine and dried with MgSO4. After removal of the solvent, the residue was purified by a flash chromatography (silica gel, hexane:ethyl acetate/1:1) to give 5-(3-chlorophenyl)-N-methoxy-N-methylbenzamide as a brown oil (5 g, 57%). To a solution of this benzamide (5 g, 17.2 mmol) in anhydrous THF was added in a dropwise fashion a solution of methyllithium in ether (1.4M, 28.6 mL, 40 mL) at −78° C. under nitrogen. After stirring for 30 minutes, the reaction mixture was treated with a saturated aqueous ammonium chloride solution (50 mL) at −78° C. Ethyl acetate (100 mL) was added, organic layer was separated, and aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed (brine) and dried (MgSO4). After removal of the solvent, the residue was purified by a flash chromatography (silica gel, hexane:ethyl acetate/2:1) to afford 1-(4-amino-3′-chloro-biphenyl-3-yl)-ethanone as a yellow solid (2 g, 47%): mp 89-90° C.; 1H-NMR (CDCl3) δ 7.89 (d, 1H, J=2.0 Hz), 7.51 (m, 2H), 7.25-7.40 (m, 3H), 6.73 (d, 1H, J=8.6 Hz), 6.38 (br, 2H), 2.65 (s, 3H); MS (EI) m/z 268 ([M+Na]+, 60%); Anal. Calcd. For C14H12ClNO: C, 68.44; H, 4.92; N, 5.70. Found: C, 68.40; H, 4.89; N, 5.61.

Workup

  1. customwas degassed
  2. customto remove the oxygen
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiontreated with brine (30 mL) and ethyl acetate (100 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×40 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried with MgSO4
  9. customAfter removal of the solvent
  10. customthe residue was purified by a flash chromatography (silica gel, hexane:ethyl acetate/1:1)

Sources & evidence

ORD record
ord-23a1b63f9f68465e9e0620ba1a09467c
Source dataset
uspto-grants-2009_08
Patent number
US07569564B2

Reaction notes

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