tert-butyl (1R,5S)-3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate → tert-Butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 72142Notes

Reaction equation

HRID 72142 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@@H:12]2[CH2:13][C:14]([CH2:16][C@H:9]1[CH2:10][CH2:11]2)=O)=[O:7])([CH3:4])[CH3:3].[BH3-]C#[N:19].[Na+]>CO>[NH2:19][CH:14]1[CH2:16][CH:9]2[N:8]([C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH:12]([CH2:11][CH2:10]2)[CH2:13]1

Participants

4

Reactant 2

HCID 688612tert-butyl (1R,5S)-3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 22570519tert-Butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylateYield 98.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred mixture of Boc-nortropinone (287 mg, 1.3 mmol), NH4OAc (1.96 g, 25.5 mmol), NaCNBH3 (800 mg, 12.7 mmol) and MeOH (20 mL) was heated at reflux for 2 h. The mixture was concentrated, the residue was diluted with 0.5 M aq NaOH (30 mL) and extracted with CH2Cl2 (2×50 mL). The combined organic phase was washed with brine (20 mL), dried over Na2SO4 and concentrated to afford tert-butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate (291 mg, quant) as a mixture of isomers. LC-MS Method 1 tR=0.88 min, m/z=227.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. concentrationThe mixture was concentrated
  4. additionthe residue was diluted with 0.5 M aq NaOH (30 mL)
  5. extractionextracted with CH2Cl2 (2×50 mL)
  6. washThe combined organic phase was washed with brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e04684fd343049fd920a9a14980402b7
Source dataset
uspto-grants-2014_09
Patent number
US08828985B2

Reaction notes

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