Hydrogen Bromide → 2-[(R)-1-(4-Chloro-3-methyl-phenyl)-propylamino]-5-fluoro-pyridine-4-carbaldehyde

HRID 1629740Notes

Reaction equation

HRID 1629740 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][C:12]2[CH:17]=[C:16]([CH:18]3OCC[O:19]3)[C:15]([F:23])=[CH:14][N:13]=2)[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:24].Br>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][C:12]2[CH:17]=[C:16]([CH:18]=[O:19])[C:15]([F:23])=[CH:14][N:13]=2)[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:24]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 67343197[(R)-1-(4-Chloro-3-methyl-phenyl)-propyl]-(4-[1,3]dioxolan-2-yl-5-fluoro-pyridin-2-yl)-amine

Product 1

HCID 866562272-[(R)-1-(4-Chloro-3-methyl-phenyl)-propylamino]-5-fluoro-pyridine-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

INT 45 (500 mg, 1.43 mmol) was dissolved in THF (20 mL) and HBr (33% in AcOH, 15 eq) was added. The resulting mixture was stirred at 70° C. until completion of the reaction. The mixture was quenched with saturated aqueous sodium bicarbonate and extracted with EtOAc. The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc) to give INT 46.

Workup

  1. customThe mixture was quenched with saturated aqueous sodium bicarbonate
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc)
  7. customto give INT 46

Sources & evidence

ORD record
ord-9b97cc0c8c0641a6855f281a77f28767
Source dataset
uspto-grants-2014_07
Patent number
US08791100B2

Reaction notes

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