N-[2-methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-N-propyl-propionamide → [2-Methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-dipropyl-amine

HRID 1354246Notes

Reaction equation

HRID 1354246 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][O:8][C:9]1[C:14]([N:15]([CH2:20][CH2:21][CH3:22])[C:16](=O)[CH2:17][CH3:18])=[CH:13][C:12]([CH3:23])=[C:11]([C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][C:25]=2[O:35][CH3:36])[N:10]=1>C1COCC1>[CH3:7][O:8][C:9]1[C:14]([N:15]([CH2:16][CH2:17][CH3:18])[CH2:20][CH2:21][CH3:22])=[CH:13][C:12]([CH3:23])=[C:11]([C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][C:25]=2[O:35][CH3:36])[N:10]=1

Participants

4

Reactant 2

HCID 21104863N-[2-methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-N-propyl-propionamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 21104797[2-Methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-dipropyl-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 1M solution of LiAlH4 in THF (0.52 ml, 0.52 mmol) at 0° C. is added to a solution of N-[2-methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-N-propyl-propionamide (94) (0.11 g, 0.26 mmol) in THF (1 ml). The mixture is stirred at 0° C. for 30 minutes and at room temperature for 15 hours. The reaction is quenched by ether containing water (5 ml) at 0° C. Water (1 ml) and EtOAc (20 ml) are added to the mixture and the suspension is stirred at room temperature for 20 minutes. MgSO4 (2 g) and Celite (2 g) are added and the mixture is stirred at room temperature for 40 minutes. The inorganic salts are removed and washed with EtOAc. The combined filtrates are concentrated under reduced pressure and the residue is purified by flash column chromatography to give [2-methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-dipropyl-amine (93); Rf (hexane/EtOAc=9:1)=0.39, MS m/z 413.4 (M+H) and [2-methoxy-6-(2-methoxy-4-trifluoromethoxy-phenyl)-5-methyl-pyridin-3-yl]-propyl-amine; Rf (hexane/EtOAc=9:1)=0.35, MS m/z 371.3 (M+H) (94)

Workup

  1. customThe reaction is quenched by ether
  2. additioncontaining water (5 ml) at 0° C
  3. additionWater (1 ml) and EtOAc (20 ml) are added to the mixture
  4. stirringthe suspension is stirred at room temperature for 20 minutes
  5. additionMgSO4 (2 g) and Celite (2 g) are added
  6. stirringthe mixture is stirred at room temperature for 40 minutes
  7. customThe inorganic salts are removed
  8. washwashed with EtOAc
  9. concentrationThe combined filtrates are concentrated under reduced pressure
  10. customthe residue is purified by flash column chromatography

Sources & evidence

ORD record
ord-5855a459f24c4eec95df17b12f7d577d
Source dataset
uspto-grants-2007_05
Patent number
US07223778B2

Reaction notes

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