Sulfuric Acid → HCID 58537915, compound

HRID 1473763Notes

Reaction equation

HRID 1473763 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH3:9])=[CH:4][C:3]=1[CH2:10][C:11]([N:13]([C:15]1([C:23]#N)[CH2:20][CH2:19][N:18]([O:21][CH3:22])[CH2:17][CH2:16]1)[CH3:14])=[O:12].S(=O)(=O)(O)[OH:26].[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH3:9])=[CH:4][C:3]=1[C:10]1[C:11](=[O:12])[N:13]([CH3:14])[C:15]2([CH2:20][CH2:19][N:18]([O:21][CH3:22])[CH2:17][CH2:16]2)[C:23]=1[OH:26]

Participants

5

Reactant 3

HCID 1118Sulfuric Acid3×HCID 14798Sodium HydroxideHCID 58537989HCID 58537989, compound

Product 1

HCID 58537915HCID 58537915, compoundYield 19.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-(2-chloro-4,5-dimethyl-phenyl)-N-(4-cyano-1-methoxy-piperidin-4-yl)-N-methyl-acetamide (compound P4.27) (1.15 g, 3.29 mmol) in methanol (˜3 ml) at 10° C. was added concentrated sulfuric acid (0.876 ml, 16.43 mmol) dropwise and the reaction mixture was stirred at room temperature overnight. After further treatment with concentrated sulfuric acid (0.876 ml, 16.43 mmol) and stirring at 80° C. overnight, additional concentrated sulfuric acid (0.876 ml, 16.43 mmol) was added and stirring continued at 90° C. over another night. The mixture was poured on ice, neutralised carefully with 30% aqueous sodium hydroxide to pH 5-6, the resulting precipitate filtered and dried to afford a first crop of product as a beige solid (225 mg). The mother liquor was concentrated, and the residue purified by chromatography on silica gel (ethyl acetate) to further deliver 462 mg of product as a yellowish solid. Yield: 687 mg of 3-(2-chloro-4,5-dimethyl-phenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diaza-spiro[4.5]dec-3-en-2-one (title compound P2.26) as a solid, mp 191-192° C.

Workup

  1. stirringstirring
  2. waitcontinued at 90° C. over another night
  3. filtrationthe resulting precipitate filtered
  4. customdried

Sources & evidence

ORD record
ord-ecae4ef50ead48f8aa18d197f064622f
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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