Methanol → (R)-tert-butyl 3-((R)-(2-aminoethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylate

HRID 218381Notes

Reaction equation

HRID 218381 reaction equation
[C:1]([CH2:3][O:4][C@@H:5]([C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[CH3:26])[C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1)#[N:2].S(C)C.CO>C1COCC1>[NH2:2][CH2:1][CH2:3][O:4][C@@H:5]([C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[CH3:26])[C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1

Participants

5

Reactant 3

HCID 887MethanolHCID 1068Dimethyl SulfideHCID 68712530(R)-tert-butyl 3-((R)-(cyanomethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylate

Product 1

HCID 58011566(R)-tert-butyl 3-((R)-(2-aminoethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (R)-tert-butyl 3-((R)-(cyanomethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylate (1.8 g, 0.005 mol) in anhydrous THF (20 ml) was heated to reflux under nitrogen. A solution of BH3.Me2S in THF was added dropwise and stirring was continued under reflux overnight. When the resulting solution was cooled to rt, MeOH was added dropwise to quench the reaction. After evaporation of the solution, the crude product was purified by column chromatography to afford (R)-tert-butyl 3-((R)-(2-aminoethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylate (1.2 g, yield 66%).

Workup

  1. temperatureto reflux under nitrogen
  2. temperatureunder reflux overnight
  3. customto quench
  4. customthe reaction
  5. customAfter evaporation of the solution
  6. customthe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-157e3212817e4c0cadce6217ce7e91ce
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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