p-Toluidine → N-(4-Methylphenyl)-2-{[(1,1-dimethylethoxy)carbonyl]amino]-6-methylbenzamide

HRID 891259Notes

Reaction equation

HRID 891259 reaction equation
CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH3:32][C:33]([CH3:49])([O:35][C:36]([NH:38][C:39]1[CH:47]=[CH:46][CH:45]=[C:44]([CH3:48])[C:40]=1[C:41]([OH:43])=O)=[O:37])[CH3:34].[NH2:50][C:51]1[CH:56]=[CH:55][C:54]([CH3:57])=[CH:53][CH:52]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:57][C:54]1[CH:55]=[CH:56][C:51]([NH:50][C:41](=[O:43])[C:40]2[C:44]([CH3:48])=[CH:45][CH:46]=[CH:47][C:39]=2[NH:38][C:36]([O:35][C:33]([CH3:32])([CH3:34])[CH3:49])=[O:37])=[CH:52][CH:53]=1

Participants

7

Reactant 5

HCID 7813p-ToluidineHCID 79724-MethylmorpholineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222451232-((tert-Butoxycarbonyl)amino)-6-methylbenzoic acid

Product 1

HCID 22245130N-(4-Methylphenyl)-2-{[(1,1-dimethylethoxy)carbonyl]amino]-6-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
18 °C

Procedure

Firstly N-methylmorpholine (6.15 mL, 5.64 g, 55.8 mmol) and then O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (10.15 g, 26.8 mmol) are added to a stirred mixture of 2-{[(1,1-dimethylethoxy)carbonyl]amino}-6-methylbenzoic acid (5.60 g, 22.3 mmol) and p-toluidine 4.78 g, 44.6 mmol) in dry dimethylformamide (110 mL) under an argon atmosphere, and stirred at 18° C. for 16 hours. The solvent is evaporated off under reduced pressure to give a residue which is treated with aqueous sodium hydrogen carbonate solution (200 mL of 10%) and extracted with dichloromethane (3×100 mL). The combined extracts are washed with aqueous citric acid solution (100 mL of 10%), dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by column chromatography on silica gel, eluent 20% ethyl acetate in hexane, and recrystallised from tert-butyl-methyl ether-hexane to give the title compound as a colourless crystalline solid, m.p. 250° C.

Workup

  1. customThe solvent is evaporated off under reduced pressure
  2. customto give a residue which
  3. extractionextracted with dichloromethane (3×100 mL)
  4. washThe combined extracts are washed with aqueous citric acid solution (100 mL of 10%)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent is evaporated off under reduced pressure
  8. customto yield the crude product which
  9. customis purified by column chromatography on silica gel, eluent 20% ethyl acetate in hexane
  10. customrecrystallised from tert-butyl-methyl ether-hexane

Sources & evidence

ORD record
ord-d743b04f7789414689fd22dde8b1f5a4
Source dataset
uspto-grants-2006_02
Patent number
US07002022B2

Reaction notes

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