Ammonium Acetate → 1-[3-(1-Aminoethyl)-5-chloro-2-methoxy-6-methylphenyl]piperidin-4-ol

HRID 510874Notes

Reaction equation

HRID 510874 reaction equation
[Cl:1][C:2]1[C:3]([CH3:20])=[C:4]([N:13]2[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15][CH2:14]2)[C:5]([O:11][CH3:12])=[C:6]([C:8](=O)[CH3:9])[CH:7]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:27].[Na+]>CO.C(#N)C>[NH2:27][CH:8]([C:6]1[C:5]([O:11][CH3:12])=[C:4]([N:13]2[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15][CH2:14]2)[C:3]([CH3:20])=[C:2]([Cl:1])[CH:7]=1)[CH3:9]

Participants

6

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 866667981-[5-Chloro-3-(4-hydroxypiperidin-1-yl)-2-methoxy-4-methylphenyl]ethanone

Product 1

HCID 866667991-[3-(1-Aminoethyl)-5-chloro-2-methoxy-6-methylphenyl]piperidin-4-ol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 1-[5-chloro-3-(4-hydroxypiperidin-1-yl)-2-methoxy-4-methylphenyl]ethanone (15 mg, 0.050 mmol), ammonium acetate (39 mg, 0.50 mmol) and sodium cyanoborohydride (6 mg, 0.1 mmol) in methanol (0.2 mL) and acetonitrile (0.2 mL) was heated at 65° C. overnight in a sealed tube. The mixture was then cooled to room temperature, quenched with saturated sodium bicarbonate and extracted with dichloromethane. The combined extracts were dried over magnesium sulfate, filtered and concentrated to dryness. The resulting crude product was used directly in next step (7 mg, 50%). LCMS calculated for C15H24ClN2O2 (M+H)+: m/z=299.1. found: 299.1.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customquenched with saturated sodium bicarbonate
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-3ca2f93113414f48a12734faf54b21f3
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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