Ammonium formate → (S)-3-Methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidine

HRID 2366028Notes

Reaction equation

HRID 2366028 reaction equation
C([N:8]1[CH2:13][CH2:12][CH2:11][C@:10]([CH3:25])([CH2:14][O:15][CH2:16][CH2:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[Pd]>[CH3:25][C@:10]1([CH2:14][O:15][CH2:16][CH2:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 66727401(S)-1-Benzyl-3-methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidine

Product 1

HCID 66727215(S)-3-Methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidineYield 83.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

(S)-1-Benzyl-3-methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidine (1.14 g, 3.3 mmol) in MeOH (11 ml) was added to a suspension of Pd/C (0.23 g) in MeOH (11 ml), followed by ammonium formate (1.03 g, 16.4 mmol). The mixture was refluxed for 2 h, after which it was cooled and filtered through Celite. The catalyst was washed with DCM and the combined organic phases were evaporated to dryness. To the residue was added brine (15 ml) and the solution was extracted with EtOAc (3×30 ml). The extracts were combined, dried, filtered and evaporated to yield 0.71 g of the debenzylated product.

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. temperatureafter which it was cooled
  3. filtrationfiltered through Celite
  4. washThe catalyst was washed with DCM
  5. customthe combined organic phases were evaporated to dryness
  6. additionTo the residue was added brine (15 ml)
  7. extractionthe solution was extracted with EtOAc (3×30 ml)
  8. customdried
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-e23251d38f694526a6c8f98df00bb4f7
Source dataset
uspto-grants-2014_04
Patent number
US08697723B2

Reaction notes

Loading…