Sodium Hydroxide → 6-Bromo-4-(oxan-4-ylamino)quinoline-3-carboxylic acid

HRID 1486915Notes

Reaction equation

HRID 1486915 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([O:14]CC)=[O:13])=[C:5]2[NH:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.[OH-].[Na+]>CCO>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([OH:14])=[O:13])=[C:5]2[NH:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 118498649Ethyl 6-bromo-4-(oxan-4-ylamino)quinoline-3-carboxylate

Product 1

HCID 1184986206-Bromo-4-(oxan-4-ylamino)quinoline-3-carboxylic acidYield 100.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

On a larger scale, ethyl 6-bromo-4-(oxan-4-ylamino)quinoline-3-carboxylate (1925 g, 5.08 mol) was charged to the vessel with EtOH (12.5 L). 2M NaOH (12.5 L, 25.03 mol) was then added with an exotherm from 22-35° C. over the 20 minute addition. The batch was heated to 70-80° C. for 17 h at which point HPLC indicated 98.3% product and <1% starting material. The batch was concentrated in vacuo to remove EtOH and returned to the vessel. A 2M HCl solution (13 L) was then added until pH 5-6 was obtained maintaining a batch temperature below 50° C. An exotherm from 20-32° C. was observed over the 40 minute addition. A precipitate formed which was slurried at 20-25° C. for 1.5 h before filtration, washing with water until pH neutral (3×7 L). The collected solid was dried under vacuum at 70° C. to give 1794 g of desired material. Analytical data was consistent with that obtained from previous batches.

Workup

  1. concentrationThe batch was concentrated in vacuo
  2. customto remove EtOH
  3. additionA 2M HCl solution (13 L) was then added until pH 5-6
  4. customwas obtained
  5. temperaturemaintaining a batch temperature below 50° C
  6. additionAn exotherm from 20-32° C. was observed over the 40 minute addition
  7. customA precipitate formed which
  8. filtrationwas slurried at 20-25° C. for 1.5 h before filtration
  9. washwashing with water until pH neutral (3×7 L)
  10. customThe collected solid was dried under vacuum at 70° C.

Sources & evidence

ORD record
ord-5d835e1edd0742e980ff5ef913b25830
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

Loading…