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

HRID 1017490Notes

Reaction equation

HRID 1017490 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-yl-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-809668c1c77a4dd29885f1bc449a4804
Source dataset
uspto-grants-2002_11
Patent number
US06479483B2

Reaction notes

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