Sodium Hydroxide → Gsk-269984A

HRID 2356619Notes

Reaction equation

HRID 2356619 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[F:29])=[C:6]([CH2:8][C:9]2[N:14]=[C:13]([C:15]([O:17]CC)=[O:16])[CH:12]=[CH:11][CH:10]=2)[CH:7]=1.[OH-].[Na+:31]>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[F:29])=[C:6]([CH2:8][C:9]2[N:14]=[C:13]([C:15]([O-:17])=[O:16])[CH:12]=[CH:11][CH:10]=2)[CH:7]=1.[Na+:31]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59384237Ethyl 6-(5-chloro-2-((4-chloro-2-fluorobenzyl)oxy)benzyl)picolinate

Product 1

HCID 23696973Gsk-269984A

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (204.7 g) was dissolved in ethanol (1.5 L) and stirred under nitrogen at reflux until all the starting material is in solution. 2M Sodium hydroxide (355 ml) was added and the solution heated under reflux for 1 hr 10 minutes. HPLC showed that there was no residual starting material. The solution was filtered and the filter washed with a ˜1:1 mixture of hot ethanol (515 ml) and water (520 ml). The combined filtrate and wash were re-heated to reflux, and water (1.5 L) was added slowly over 5 minutes. The solution was then cooled to 20+/−5° C. over 2 hours and stirred for 1 hour. The product was then filtered off and washed with ethanol:water (1:1, 1030 ml), then ethanol:water (˜1:3; 385 ml ethanol:1.15 L water). The resulting solid was dried to a constant weight at 60° C. under vacuum, to give the title compound. (186 g).

Workup

  1. temperatureat reflux until all the starting material
  2. temperaturethe solution heated
  3. temperatureunder reflux for 1 hr 10 minutes
  4. filtrationThe solution was filtered
  5. washthe filter washed with a ˜1:1 mixture of hot ethanol (515 ml) and water (520 ml)
  6. washThe combined filtrate and wash
  7. temperaturewere re-heated
  8. temperatureto reflux
  9. additionwater (1.5 L) was added slowly over 5 minutes
  10. temperatureThe solution was then cooled to 20+/−5° C. over 2 hours
  11. stirringstirred for 1 hour
  12. filtrationThe product was then filtered off
  13. washwashed with ethanol:water (1:1, 1030 ml)
  14. customThe resulting solid was dried to a constant weight at 60° C. under vacuum

Sources & evidence

ORD record
ord-23c5dface5d34f8a82a808ac6dd77502
Source dataset
uspto-grants-2010_07
Patent number
US07759369B2

Reaction notes

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