HCID 66876149, compound → HCID 66875875, compound

HRID 1019278Notes

Reaction equation

HRID 1019278 reaction equation
C([N:8]1[C@H:13]2[CH2:14][CH2:15][C@@H:9]1[CH:10]([C:17]([O:19][CH3:20])=[O:18])[C:11](=[O:16])[CH2:12]2)C1C=CC=CC=1>C(O)(=O)C.[Pd]>[O:16]=[C:11]1[CH2:12][C@H:13]2[NH:8][C@H:9]([CH2:15][CH2:14]2)[CH:10]1[C:17]([O:19][CH3:20])=[O:18]

Participants

4

Reactant 1

HCID 66876149HCID 66876149, compound

Product 1

HCID 66875875HCID 66875875, compoundYield 97.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of methyl (1R,5S)-8-benzyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate ((−)-2b) (818 mg, 2.99 mmol) in acetic acid (10 ml) was added 10% Pd-C (a catalyst), and the resulting mixture was stirred under a hydrogen atmosphere for 10 hours. After completion of the reaction, the mixture was filtered with Celite and the filtrate was concentrated in vacuo. The residue was adjusted to pH 8.0-8.5 with a saturated aqueous sodium hydrogen-carbonate solution and extracted with chloroform. The extract was dried over Na2SO4, filtered and then concentrated in vacuo, and the thus obtained crude product was purified by a silica gel column chromatography (CHCl3:MeOH=30:1) to obtain 536.5 mg of methyl (1R,5S)-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate. In this case, the yield was 98 mol %. Then, to a methanol (20 ml) solution of this compound (281 mg, 1.54 mmol) were added a 37% formaldehyde solution (213 μl, 7.67 mmol), formic acid (579 μl, 15.4 mmol) and paraformaldehyde (200 mg), and the resulting mixture was refluxed for 17 hours. After completion of the reaction, the reaction mixture was adjusted to pH 8.0-8.5 with a saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform. The extract was dried over Na2SO4, filtered and then concentrated in vacuo, and the thus obtained crude product was purified by a silica gel column chromatography (CHCl3:MeOH=50:1) to obtain 274 mg of methyl (1R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate. The yield from the above two steps was 88 mol %.

Workup

  1. customAfter completion of the reaction
  2. filtrationthe mixture was filtered with Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. extractionextracted with chloroform
  5. dry with materialThe extract was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe thus obtained crude product
  9. customwas purified by a silica gel column chromatography (CHCl3:MeOH=30:1)

Sources & evidence

ORD record
ord-384c5d85c78642d880c8d3112df7e1cc
Source dataset
uspto-grants-2002_11
Patent number
US06486323B1

Reaction notes

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