Sulfuric Acid → 6-(1,1-Dioxido-4-thiomorpholinyl)-4-(4-fluoro-2-methylphenyl)nicotinamide

HRID 131114Notes

Reaction equation

HRID 131114 reaction equation
[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[CH3:24])=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][S:12](=[O:16])(=[O:15])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)#[N:2].C1(C)C=CC=CC=1.S(=O)(=O)(O)[OH:33].[OH-].[Na+]>O>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C:4]2[CH:5]=[C:6]([N:9]3[CH2:14][CH2:13][S:12](=[O:15])(=[O:16])[CH2:11][CH2:10]3)[N:7]=[CH:8][C:3]=2[C:1]([NH2:2])=[O:33])=[C:18]([CH3:24])[CH:19]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 1140TolueneHCID 14798Sodium HydroxideHCID 573550096-(1,1-Dioxo-1lambda~6~,4-thiazinan-4-yl)-4-(4-fluoro-2-methylphenyl)pyridine-3-carbonitrile

Product 1

HCID 116749676-(1,1-Dioxido-4-thiomorpholinyl)-4-(4-fluoro-2-methylphenyl)nicotinamideYield 100.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-cyano-4-(4-fluoro-2-methylphenyl)-2-(1,1-dioxo-thiomorpholin-4-yl)pyridine (14.80 g, 42.85 mmol), 15 mL of toluene, and 15 mL (27.6 g, 281 mmol) of concentrated sulfuric acid was heated in a 500-mL flask at 70° C. for 12 hours. The mixture was cooled and quenched with 150 mL cold H2O. A solution of 22.8 g (570 mmol) of sodium hydroxide in 200 mL of H2O was added dropwise at 25–30° C. over 15 minutes. The precipitate was filtered, washed with H2O, and dried to afford 15.68 g (100.7%) of 4-(4-fluoro-2-methylphenyl)-6-(1,1-dioxo-thiomorpholin-4-yl)pyridine-3-carboxamide as a colorless solid (2 wt % toluene remains).

Workup

  1. temperatureThe mixture was cooled
  2. customquenched with 150 mL cold H2O
  3. filtrationThe precipitate was filtered
  4. washwashed with H2O
  5. customdried

Sources & evidence

ORD record
ord-666bda28d35f4ffbb5cf1fa9ebae826d
Source dataset
uspto-grants-2008_06
Patent number
US07384939B2

Reaction notes

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