Sulfuric Acid → 6-Morpholin-4-yl-4-o-tolyl-nicotinamide

HRID 380763Notes

Reaction equation

HRID 380763 reaction equation
C([NH:8][C:9](=[O:29])[C:10]1[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])=[CH:14][C:13]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[N:12][CH:11]=1)C1C=CC=CC=1.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CS(O)(=O)=O>[N:23]1([C:13]2[CH:14]=[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH3:22])[C:10]([C:9]([NH2:8])=[O:29])=[CH:11][N:12]=2)[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 1118Sulfuric Acid2×HCID 10340Sodium CarbonateHCID 12167316N-benzyl-6-morpholin-4-yl-4-o-tolyl-nicotinamide

Product 1

HCID 111622966-Morpholin-4-yl-4-o-tolyl-nicotinamideYield 39.1%

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidSolvent

Procedure

0.5 g (1.29 mMol) N-Benzyl-6-morpholin-4-yl-4-o-tolyl-nicotinamide was dissolved in 2.5 ml methanesulfonic acid and 0.25 ml sulfuric acid and heated to 100° C. for 1 hour. A second portion of 0.25 ml sulfuric acid was added and heating was pursued for 22 hours. After cooling to room temperature, the reaction mixture was poured onto 75 ml aqueous saturated sodium carbonate, cooled with ice and extracted with ethyl acetate. The combined organic extracts were washed with aqueous saturated sodium carbonate and brine, dried (Na2SO4) and concentrated. The residue was flash chromatographed (eluent: dichloromethane/methanol 95:5) to yield 0.15 g (39%) 6-morpholin-4-y1-4-o-tolyl-nicotinamide as a yellow resin.

Workup

  1. temperatureheating
  2. temperaturecooled with ice
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with aqueous saturated sodium carbonate and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customchromatographed (eluent: dichloromethane/methanol 95:5)

Sources & evidence

ORD record
ord-779678898ebc44c4afc910d1c9587486
Source dataset
uspto-grants-2001_10
Patent number
US06303790B1

Reaction notes

Loading…