HCID 59536616, compound → (S)-3-((S)-1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidine

HRID 1922184Notes

Reaction equation

HRID 1922184 reaction equation
C([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([O:18][C:19]2[C:20]([CH3:27])=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)[CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:9]1)C1C=CC=CC=1>C(O)C.[Pd]>[CH3:26][O:25][C:22]1[N:21]=[C:20]([CH3:27])[C:19]([O:18][C@H:13]([C@H:10]2[CH2:11][CH2:12][NH:8][CH2:9]2)[CH2:14][CH:15]([CH3:17])[CH3:16])=[CH:24][CH:23]=1

Participants

4

Reactant 1

HCID 59536616HCID 59536616, compound

Product 1

HCID 59536635(S)-3-((S)-1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidineYield 97.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

Charge a 400 mL stainless steel autoclave with 20% by weight Pd/C (10%, wet, 820 mg) followed by a solution of (S)-1-benzyl-3-((S)-1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidine (4.1 g, 11.126 mmoles) in ethanol (82 mL). Purge with H2 gas (3×50 PSI), then charge the vessel with H2 gas (50 PSI). Heat the reaction mixture to 60° C.1 and stir at 60° C. for 24 hours. The pressure of the vessel increases to ˜55 PSI at 60° C. and the vessel is refilled with H2 gas as needed. Allow the reaction mixture to cool to room temperature, filter through a medium fritted funnel charged with celite (wet with ethanol), and wash with ethanol (˜80 mL). Concentrate under reduced pressure to give (S)-3-((S)-1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidine as a light yellow oil (3.02 g, 10.848 mmoles, 97.5% yield). 1H NMR (300 MHz, CDCl3) δ 7.12 (d, 1H, J=8.79 Hz), 6.50 (d, 1H, 8.79 Hz), 4.2 (aq, 1H, Ja=7.03 Hz, Jb=5.27 Hz), 3.87 (s, 3H), 3.08-2.94 (m, 2H), 2.94-2.82 (m, 1H), 2.82-2.70 (m, 1H), 2.50-2.26 (m, 3H), 2.36 (s, 3H), 1.94-1.78 (m, 1H), 1.78-1.52 (m, 3H), 1.44-1.30 (m, 1H), 0.898 (at, 6H, Ja=6.45 Hz, Jb=7.03 Hz). LC/MS=279.3 (M+1).

Workup

  1. customPurge with H2 gas (3×50 PSI)
  2. additioncharge the vessel with H2 gas (50 PSI)
  3. temperatureThe pressure of the vessel increases to ˜55 PSI at 60° C.
  4. additionthe vessel is refilled with H2 gas
  5. temperatureto cool to room temperature
  6. filtrationfilter through a medium fritted funnel
  7. additioncharged with celite (wet with ethanol)
  8. washwash with ethanol (˜80 mL)
  9. concentrationConcentrate under reduced pressure

Sources & evidence

ORD record
ord-bc83cfb61c014e8594d63c56a97d6aa8
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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