Hydrochloric Acid → 1007377-55-0

HRID 538655Notes

Reaction equation

HRID 538655 reaction equation
C([O:3][C:4](=[O:23])[CH2:5][NH:6][C:7]([C:9]1[C:14]([OH:15])=[CH:13][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[CH:11][N:10]=1)=[O:8])C.[OH-].[Na+].Cl>C1COCC1>[F:22][C:18]1[CH:17]=[C:16]([C:12]2[CH:13]=[C:14]([OH:15])[C:9]([C:7]([NH:6][CH2:5][C:4]([OH:23])=[O:3])=[O:8])=[N:10][CH:11]=2)[CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 49848229HCID 49848229, compound

Product 1

HCID 498484851007377-55-0Yield 55.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of {[5-(3-fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid ethyl ester, 5, (226 g, 0.71 mol) in THF (1 L) at room temperature was added an aqueous solution of sodium hydroxide (1 M, 2 L) while maintaining the internal reaction temperature below 25° C. The progress of the reaction was monitored by TLC. After 20-30 minutes, the reaction was completed. The pH of the reaction solution was adjusted using concentrated HCl to 5-5.5 while maintaining the internal temperature below 25° C. The reaction mixture was filtered to remove insoluble matter and the filtrate was concentrated by rotary evaporation at up to 40° C. bath temperature until all THF was removed. The resulting solid was collected by vacuum filtration and washed with water (1 L). The solid was then dissolved in a mixture of water (1.5 L) and THF (1.5 L) at room temperature. The pH was adjusted from approximately 5 to approximately 2-2.25 with concentrated HCl. The resulting mixture was stirred for 30 minutes, after which time the pH was confirmed in the range of 2-2.5. The biphasic mixture was concentrated by rotary evaporation at up to 40° C. bath temperature until the removal of THF ceased. The resulting solid was filtered, washed with water (2×1 L), and dried to afford 115 g (55.8% yield) of the desired product as a white solid. MP: 182-184° C.; MS (ESI−): m/z 289 (M−1); 1H NMR (300 MHz, DMSO-d6) δ 12.90 (s, 1H), 12.38 (s, 1H), 9.39-9.37 (t, J=6.3 Hz, 1H), 8.55 (s, 1H), 7.80-7.67 (m, 2H), 7.59-7.52 (m, 1H), 7.34-7.27 (m, 1H), 4.02-3.99 (m, 2H), 3.51 (s, 1H).

Workup

  1. temperaturewhile maintaining the internal reaction temperature below 25° C
  2. temperaturewhile maintaining the internal temperature below 25° C
  3. filtrationThe reaction mixture was filtered
  4. customto remove insoluble matter
  5. concentrationthe filtrate was concentrated by rotary evaporation at up to 40° C. bath temperature until all THF
  6. customwas removed
  7. filtrationThe resulting solid was collected by vacuum filtration
  8. washwashed with water (1 L)
  9. dissolutionThe solid was then dissolved in a mixture of water (1.5 L) and THF (1.5 L) at room temperature
  10. concentrationThe biphasic mixture was concentrated by rotary evaporation at up to 40° C. bath temperature
  11. customuntil the removal of THF
  12. filtrationThe resulting solid was filtered
  13. washwashed with water (2×1 L)
  14. customdried

Sources & evidence

ORD record
ord-13f076103d9d4fe688aa9463e34856fb
Source dataset
uspto-grants-2014_10
Patent number
US08865748B2

Reaction notes

Loading…