HCID 11858494, compound → 4-Benzyloxy-2-((R)-2-hydroxy-propylamino)benzaldehyde

HRID 2121866Notes

Reaction equation

HRID 2121866 reaction equation
O.[PH2]([O-])=O.[Na+].[CH2:6]([O:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#N)=[C:16]([NH:22][CH2:23][C@H:24]([OH:26])[CH3:25])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.N1C=CC=CC=1CC(O)=[O:35].O>[Ni]>[CH2:6]([O:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:35])=[C:16]([NH:22][CH2:23][C@H:24]([OH:26])[CH3:25])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 11858494HCID 11858494, compoundHCID 69477857Pyridine-acetic acid waterHCID 178418950HCID 178418950, compound

Product 1

HCID 113466744-Benzyloxy-2-((R)-2-hydroxy-propylamino)benzaldehydeYield 90%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Conditions

Temperature
45 °C

Procedure

Sodium hypophosphite hydrate (986 g, 11.2 mol) and Raney nickel (500 g of a 50% aqueous suspension) were added to a solution of the product from Step B (790 g, 2.8 mol) in a 2:1:1 mixture of pyridine-acetic acid-water (7 L). The mixture was stirred at 45° C. for 7 h, then cooled to 25° C. overnight and filtered through a filter-aide rinsing with water and ethyl acetate. The filtrate was washed with saturated sodium hydrogenphosphate to pH 5, water and brine, dried over sodium sulfate and concentrated. During concentration, 4 L of heptane was added to azeotropically remove pyridine. After 8 L of solvent had been removed the product solidified. Heptane (5 L) was added and the solid was triturated, isolated by filtration and vacuum dried at 35° C. to yield the desired product (722 g, 90%).

Workup

  1. temperaturecooled to 25° C. overnight
  2. filtrationfiltered through a filter-aide
  3. washrinsing with water and ethyl acetate
  4. washThe filtrate was washed with saturated sodium hydrogenphosphate to pH 5, water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. concentrationDuring concentration, 4 L of heptane
  8. additionwas added to azeotropically remove pyridine
  9. customAfter 8 L of solvent had been removed the product
  10. additionHeptane (5 L) was added
  11. customthe solid was triturated
  12. customisolated by filtration and vacuum
  13. customdried at 35° C.

Sources & evidence

ORD record
ord-cc2af5048216413d9d12f10dfa09cd45
Source dataset
uspto-grants-2004_02
Patent number
US06696476B2

Reaction notes

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