Hydrochloric Acid → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(6-neopentyl-1,2,3,4-tetrahydroquinolin-4-YL)amino]propyl}acetamide

HRID 1985097Notes

Reaction equation

HRID 1985097 reaction equation
[C:1]([NH:4][C@@H:5]([CH2:35][C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[C:38]([F:43])[CH:37]=1)[C@H:6]([OH:34])[CH2:7][NH:8][CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:17]=2)[N:12](C(OCC2C=CC=CC=2)=O)[CH2:11][CH2:10]1)(=[O:3])[CH3:2].Cl>CCO.[Pd]>[F:42][C:40]1[CH:41]=[C:36]([CH:37]=[C:38]([F:43])[CH:39]=1)[CH2:35][C@H:5]([NH:4][C:1](=[O:3])[CH3:2])[C@H:6]([OH:34])[CH2:7][NH:8][CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:17]=2)[NH:12][CH2:11][CH2:10]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58909414HCID 58909414, compound

Product 1

HCID 10411894N-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(6-neopentyl-1,2,3,4-tetrahydroquinolin-4-YL)amino]propyl}acetamideYield 50.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of benzyl 4-{[(2R,3S)-3-(acetylamino)-4-(3,5-difluorophenyl)-2-hydroxybutyl]amino}-6-neopentyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.242 g) in EtOH (30 mL) was added 1N HCl (1.0 mL) and 10% palladium on carbon (0.030 g). The mixture was degassed with N2 for five minutes. The mixture was placed on a hydrogenation apparatus under 47 psi of H2 and was shaken for 4.5 hours. The palladium was filtered off using Celite and the solvent was concentrated under reduced pressure. The residue was then partitioned between water and ethyl acetate and the organic layers were washed with aqueous sodium bicarbonate, dried with magnesium sulfate, filtered, and concentrated. A silica gel column using 4% MeOH in dichloromethane with 0.25% NH4OH as the solvent solution gave 0.095 g of the title compound. MS (ESI+) for C26H35F2N3O2 m/z 460.27 (M+H)+.

Workup

  1. customThe mixture was degassed with N2 for five minutes
  2. filtrationThe palladium was filtered off
  3. concentrationthe solvent was concentrated under reduced pressure
  4. customThe residue was then partitioned between water and ethyl acetate
  5. washthe organic layers were washed with aqueous sodium bicarbonate
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e927eb09698f4ec0a53d944799bcc514
Source dataset
uspto-grants-2009_06
Patent number
US07544717B2

Reaction notes

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