Sodium Carbonate → Rilopirox

HRID 2291722Notes

Reaction equation

HRID 2291722 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[O:5][C:4](=O)[CH:3]=1.S([O-])([O-])(=O)=O.[OH:30][NH3+:31].O[NH3+].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[OH:30][N:31]1[C:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)=[CH:7][C:2]([CH3:1])=[CH:3][C:4]1=[O:5]

Participants

5

Reactant 3

HCID 10340Sodium Carbonate2×HCID 24846Hydroxylamine sulfate2×HCID 14053977HCID 14053977, compound

Product 1

HCID 71778Rilopirox

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

171.4 g (0.5 mole) of 4-methyl-6-[4-(4-chlorophenoxy)phenoxymethyl]-2-pyrone in 50 ml of toluene were heated to 80° C. Then 59.9 g (0.36 mole) of hydroxylammonium sulfate and 38.3 g (0.36 mole) of sodium carbonate were added. 10 minutes later a further 59.9 g (0.36 mole) of hydroxylammonium sulfate and 38.3 g (0.36 mole) of sodium carbonate were added. After about 4 hours the heating was removed and, at about 40° C., 500 ml of methylene chloride were added. The dissolved reaction product was then filtered off from the insoluble salts. The filtrate was then dried over sodium sulfate, and the methylene chloride was evaporated off. When the residue was stirred with 500 ml of ethyl acetate, the reaction product crystallized out. For final purification, the 1-hydroxy-4-methyl-6-[4-(4-chlorophenoxy)phenoxymethyl]-2-pyridone was recrystallized from dimethylformamide. Yield 80.5 g (45%); melting point 168°-170° C.

Workup

  1. customAfter about 4 hours the heating was removed and, at about 40° C.
  2. addition500 ml of methylene chloride were added
  3. customThe dissolved reaction product
  4. filtrationwas then filtered off from the insoluble salts
  5. dry with materialThe filtrate was then dried over sodium sulfate
  6. customthe methylene chloride was evaporated off
  7. customthe reaction product crystallized out
  8. customFor final purification
  9. customthe 1-hydroxy-4-methyl-6-[4-(4-chlorophenoxy)phenoxymethyl]-2-pyridone was recrystallized from dimethylformamide

Sources & evidence

ORD record
ord-7ed1e6fc0a184d9db537060abceecd7a
Source dataset
uspto-grants-1989_01
Patent number
US04797409

Reaction notes

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