Sodium Hydroxide → 3-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine

HRID 411517Notes

Reaction equation

HRID 411517 reaction equation
[C:1]([BH3-])#[N:2].[Na+].[CH2:5]([N:12]1[CH2:18][CH:17]2[C:19](=O)[CH:14]([CH2:15][CH2:16]2)[CH2:13]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Cl.CN.[OH-].[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH2:5]([N:12]1[CH2:13][CH:14]2[CH:19]([NH:2][CH3:1])[CH:17]([CH2:16][CH2:15]2)[CH2:18]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 6364545Methylamine hydrochlorideHCID 156391343-Benzyl-3-azabicyclo(3.2.1)octan-8-one

Product 1

HCID 185410303-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amineYield 49%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of sodium cyanoborohydride (35.0 g, 0.557 mol) and zinc chloride (37.9 g, 0.278 mol) in methanol (500 mL) was added dropwise to a mechanically stirred mixture of 3-benzyl-3-azabicyclo[3.2.1]octan-8-one (Preparation A; 120 g, 0.557 mol) and methylamine hydrochloride (151 g, 2.23 mol) in methanol (1.0 L) at 25° C. under nitrogen. After 2.5 h of stirring, 6 N NaOH (90 mL) was added dropwise. The mixture was filtered through a pad of Celite®, washing with methanol (500 mL). The filtrate was concentrated in vacuo. Water (500 mL) was added, and the aqueous mixture was extracted with ethyl acetate (3×500 mL). The combined organic extracts were dried (Na2SO4), and concentrated in vacuo. The residue was chromatographed, eluting with methanol dichloromethane (1:10), to afford 63.0 g (49%) of the sub-title compound as a solid.

Workup

  1. customPreparation A
  2. customat 25° C.
  3. filtrationThe mixture was filtered through a pad of Celite®
  4. washwashing with methanol (500 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. additionWater (500 mL) was added
  7. extractionthe aqueous mixture was extracted with ethyl acetate (3×500 mL)
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed
  11. washeluting with methanol dichloromethane (1:10)

Sources & evidence

ORD record
ord-dd20e89bb4d74da892ac2debda183ca5
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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