Hydrochloric Acid → HCID 67297613, compound

HRID 876548Notes

Reaction equation

HRID 876548 reaction equation
[CH3:1][C:2]1([CH3:9])[O:6][C@H:5]([CH2:7][OH:8])[CH2:4][O:3]1.[H-].[Na+].Br[C:13]1[N:21]=[CH:20][CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=[O:16].Cl>C1COCC1.[Cl-].[Na+].O>[CH3:1][C:2]1([CH3:9])[O:6][C@H:5]([CH2:7][O:8][C:13]2[N:21]=[CH:20][CH:19]=[CH:18][C:14]=2[C:15]([OH:17])=[O:16])[CH2:4][O:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 2332622-Bromopyridine-3-carboxylic acidHCID 736056(R)-Solketal

Product 1

HCID 67297613HCID 67297613, compoundYield 95.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methanol 54 (1.8 mL, 14.9 mmol) was added to a room temperature suspension of NaH (392 mg, 16.3 mmol) in THF (30 mL). The reaction mixture was stirred at room temperature for 30 min and 2-bromo-nicotinic acid 53 (1 g, 4.95 mmol) was added. The reaction mixture was heated at reflux for 12 h. After cooling to room temperature, 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 and concentrated. The crude product was recrystallized from pentane/EtOAc to give 55 (1.2 g, 92% 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.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 12 h
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with EtOAc
  5. customThe combined organics were dried
  6. concentrationconcentrated
  7. customThe crude product was recrystallized from pentane/EtOAc

Sources & evidence

ORD record
ord-32ce10d286ad490f8aab995d4a4aa2a2
Source dataset
uspto-grants-2015_03
Patent number
US08987258B2

Reaction notes

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