Water → {(1R,3S)-5-Isopropoxy-6-methyl-3-[1-(2-phenyl-butyl)-piperidin-4-yl]-isochroman-1-ylmethyl}methyamine

HRID 2074429Notes

Reaction equation

HRID 2074429 reaction equation
[CH:1]([O:4][C:5]1[C:14]([CH3:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][C@@H:8]([CH:20]1[CH2:25][CH2:24][N:23]([C:26](=O)[CH:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:28][CH3:29])[CH2:22][CH2:21]1)[O:9][C@H:10]2[CH2:16][NH:17][CH:18]=O)([CH3:3])[CH3:2].C(Cl)Cl.[OH-].[Na+].O>[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)C>[CH:1]([O:4][C:5]1[C:14]([CH3:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][C@@H:8]([CH:20]1[CH2:21][CH2:22][N:23]([CH2:26][CH:27]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:28][CH3:29])[CH2:24][CH2:25]1)[O:9][C@H:10]2[CH2:16][NH:17][CH3:18])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6344Dichloromethane2×HCID 14798Sodium HydroxideHCID 86612296N-{(1R,3S)-5-Isopropoxy-6-methyl-3-[1-(2-phenyl-butyryl)-piperidin-4-yl]-isochroman-1-ylmethyl}formamide

Product 1

HCID 67091130{(1R,3S)-5-Isopropoxy-6-methyl-3-[1-(2-phenyl-butyl)-piperidin-4-yl]-isochroman-1-ylmethyl}methyamine

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21226445Aluminium lithium hydrideSolvent

Procedure

Dissolve N-{(1R,3S)-5-isopropoxy-6-methyl-3-[1-(2-phenyl-butyryl)-piperidin-4-yl]-isochroman-1-ylmethyl}formamide (0.10 g, 0.20 mmole) in 1M lithium aluminum hydride in diethyl ether (1.5 mL) and bring to reflux. After 3.5 hr cool to room temperature, add methylene chloride (2 mL) followed by dropwise addition of 10% NaOH until no further reaction is observed. Add 2 mL of methylene chloride and 4 mL of water and filter reaction mixture and wash the filter cake with additional methylene chloride and water. Combine the organic phases and dry over Na2SO4. Purify the crude product on a 4 g silica gel column (eluting with methylene chloride and then methylene chloride:methanol:ammonium hydroxide 89:10:1). Collect the appropriate fractions and concentrate to obtain the title compound. It was used without further purification in the next step.

Workup

  1. temperatureto reflux
  2. filtrationfilter
  3. customreaction mixture
  4. washwash the filter cake with additional methylene chloride and water
  5. dry with materialdry over Na2SO4
  6. customPurify the crude product on a 4 g silica gel column (
  7. washeluting with methylene chloride
  8. customCollect the appropriate fractions
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-09f73a00382f4854bcb3e21b9996e0f9
Source dataset
uspto-grants-2011_04
Patent number
US07919508B2

Reaction notes

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