Hydrochloric Acid → HCID 58477293, compound

HRID 520475Notes

Reaction equation

HRID 520475 reaction equation
[CH3:1][C:2]1([CH3:9])[O:6][CH:5]([CH2:7][OH:8])[CH2:4][O:3]1.[H-].[Na+].Br[C:13]1[N:18]=[C:17]([C:19]([OH:21])=[O:20])[CH:16]=[CH:15][CH:14]=1.Cl>C1COCC1.[Cl-].[Na+].O.O>[CH3:1][C:2]1([CH3:9])[O:6][CH:5]([CH2:7][O:8][C:13]2[N:18]=[C:17]([C:19]([OH:21])=[O:20])[CH:16]=[CH:15][CH:14]=2)[CH2:4][O:3]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7528SolketalHCID 24758Sodium hydrideHCID 5939196-Bromopyridine-2-carboxylic acid

Product 1

HCID 58477293HCID 58477293, compoundYield 66.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Solketal 58 (23.5 g, 178 mmol) was added to a suspension of NaH (7.1 g, 178 mmol, 60 wt % dispersion in mineral oil) in THF (400 mL) cooled to 0° C. The reaction mixture was stirred at room temperature for 1 h and 6-bromopicolinic acid 57 (12 g, 59.4 mmol) was added. The reaction mixture was heated at reflux for 1.5 h. After cooling to room temperature, H2O (50 mL) was added and the pH was adjusted to 3 by the addition of 3 N HCl. The mixture was poured into brine and extracted with EtOAc. The combined organics were dried (Na2SO4) and concentrated. The crude product was recrystallized from pentane/EtOAc to give 59 (10 g, 66% yield). The acetonide protecting group could be removed after coupling with the appropriate aniline by treatment with EtOH/3 N HCl (4:1) at reflux for 12 h. The acetonide protecting group could be removed after coupling with the appropriate aniline by treatment with EtOH/3 N HCl (4:1) at reflux for 12 h.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1.5 h
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was recrystallized from pentane/EtOAc

Sources & evidence

ORD record
ord-49b2758b1cac434fb42e44cfab10fe96
Source dataset
uspto-grants-2016_05
Patent number
US09326986B2

Reaction notes

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