Sodium Hydroxide → HCID 58294438, compound

HRID 521022Notes

Reaction equation

HRID 521022 reaction equation
S(Cl)(Cl)=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([C:13]2[C:14]([C:19]([OH:21])=O)=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:10]=[CH:11][CH:12]=1.[Cl-].[Al+3].[Cl-].[Cl-].[OH-].[Na+]>ClCCl.O.CN(C)C=O>[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]2[C:19](=[O:21])[C:14]3[C:13]([C:9]=2[CH:8]=1)=[CH:18][CH:17]=[CH:16][N:15]=3

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 52983911HCID 52983911, compound

Product 1

HCID 58294438HCID 58294438, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

Thionyl chloride (0.95 L) is added over 30 min to a solution of 3-(3-methoxy-phenyl)-pyridine-2-carboxylic acid (crude product; 2.0 kg) and N,N-dimethylformamide (34 mL) in dichloromethane (9 L) at 40° C. The addition vessel is rinsed with dichloromethane (1 L) and the solution is stirred at 40° C. for 2 h. The solution is diluted with toluene (10 L) and most of the solvent is evaporated (residual toluene ca. 2 L). Dichloromethane (10 L) is added to obtain a homogeneous solution. The solution is heated to 35° C. and added over 30 min to a vessel charged with aluminum chloride (1.75 kg) and dichloromethane (10 L) while keeping mild reflux. The mixture is stirred at 40° C. for 30 min and then cooled to 0° C. Water (4 L) is added at such a rate that the solution temperature maintained below 40° C. The aqueous layer is adjusted to pH value 2.5-3.5 using 2 M aqueous NaOH solution and the resulting mixture is stirred for 15 min. The organic layer is separated and the aqueous layer is extracted with dichloromethane (2×). The combined organic phase is concentrated (to ca. 10 L) and toluene (10 L) is added to the residue. The residual amount of dichloromethane is evaporated and the precipitate is separated and washed with toluene (2 L) and heptane (4 L) and dried under vacuum to give the title compound.

Workup

  1. washThe addition vessel is rinsed with dichloromethane (1 L)
  2. additionThe solution is diluted with toluene (10 L) and most of the solvent
  3. customis evaporated (residual toluene ca. 2 L)
  4. additionDichloromethane (10 L) is added
  5. customto obtain a homogeneous solution
  6. temperatureThe solution is heated to 35° C.
  7. additionadded over 30 min to a vessel
  8. stirringThe mixture is stirred at 40° C. for 30 min
  9. temperaturecooled to 0° C
  10. temperaturemaintained below 40° C
  11. stirringthe resulting mixture is stirred for 15 min
  12. customThe organic layer is separated
  13. extractionthe aqueous layer is extracted with dichloromethane (2×)
  14. concentrationThe combined organic phase is concentrated (to ca. 10 L) and toluene (10 L)
  15. additionis added to the residue
  16. customThe residual amount of dichloromethane is evaporated
  17. customthe precipitate is separated
  18. washwashed with toluene (2 L) and heptane (4 L)
  19. customdried under vacuum

Sources & evidence

ORD record
ord-567fec356ad046708a2a7e16880785ec
Source dataset
uspto-grants-2016_05
Patent number
US09328072B2

Reaction notes

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