Hydrochloric Acid → HCID 71075672, compound

HRID 2283186Notes

Reaction equation

HRID 2283186 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([OH:20])[C:11]([NH:14][CH2:15][C:16]([O:18]C)=[O:17])=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.O1CCCC1.[OH-].[Na+].Cl>CCCCCC.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([OH:20])[C:11]([NH:14][CH2:15][C:16]([OH:18])=[O:17])=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86674623HCID 86674623, compound

Product 1

HCID 71075672HCID 71075672, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a 20 L reactor equipped with a mechanical stirrer, condenser, thermometer and nitrogen inlet was charged methyl {[5-(3-chlorophenyl)-3-hydroxypyridin-2-yl]amino}-acetate, 4, (440 g, 1.42 mol), tetrahydrofuran (3912 g, 4400 mL) and 1 M NaOH (4400 mL). The mixture was stirred for 2 hours at room temperature after which it was determined by TLC analysis using hexane/ethyl acetate (6:3) as the mobile phase and UV 435 nm to visualize the reaction components that the reaction was complete. The reaction solution was acidified to a pH of 2 with slow addition of 2M HCl (2359 g). The resulting mixture was concentrated under reduced pressure to a volume of about 7.5 L. Ware (2210 g) was added and the solution cooled to ambient temperature and agitated for 18 hours. The solid product was isolated by filtration and washed with water (6 L). the crude product was transferred back into the reactor and triturated with 2215 g o deionized water at 70° C. for 16 hours. The mixture was cooled to ambient temperature, The solid product was isolated by filtration and washed with water (500 mL) and dried under reduced pressure at 70° C. for 20 hours to afford 368 g (87% yield) of the desired product as an off-white solid. Purity by HPLC was 99.3%. 1H NMR (DMSO-d6) δ 12.84 (s, 1H), 12.39 (s, 1H), 9.39 (t, 1H), 8.56 (d, 1H), 7.94 (s, 1H), 7.81 (m, 2H), 7.55 (q, 2H), and 4.02 (d, 2H).

Workup

  1. customTo a 20 L reactor equipped with a mechanical stirrer, condenser
  2. customthe reaction components that the reaction
  3. concentrationThe resulting mixture was concentrated under reduced pressure to a volume of about 7.5 L
  4. additionWare (2210 g) was added
  5. temperaturethe solution cooled to ambient temperature
  6. stirringagitated for 18 hours
  7. customThe solid product was isolated by filtration
  8. washwashed with water (6 L)
  9. customtriturated with 2215 g o deionized water at 70° C. for 16 hours
  10. temperatureThe mixture was cooled to ambient temperature
  11. customThe solid product was isolated by filtration
  12. washwashed with water (500 mL)
  13. customdried under reduced pressure at 70° C. for 20 hours

Sources & evidence

ORD record
ord-cad0aa3765314e6e9912304963a6cdcf
Source dataset
uspto-grants-2015_09
Patent number
US09145366B2

Reaction notes

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