Methanol → Tert-butyl 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate hydrochloride

HRID 1351124Notes

Reaction equation

HRID 1351124 reaction equation
[ClH:1].C([N:9]1[CH2:16][CH:15]2[O:17][CH:11]([CH2:12][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]2)[CH2:10]1)C1C=CC=CC=1.CO>C(#N)C>[ClH:1].[CH:11]12[O:17][CH:15]([CH2:16][NH:9][CH2:10]1)[CH2:14][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:12]2

Participants

4

Reactant 2

HCID 887MethanolHCID 18540371335620-99-0

Product 1

HCID 18540411Tert-butyl 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Hydrochloride salt from step (iii) above (146 g, 0.411 mol) and 20% Pd(OH)2-C (7.5 g) were charged to a Parr hydrogenator bottle. Methanol (0.5 L) was added and the bottle was shaken vigorously under an atmosphere of hydrogen at 3.5 bar. The reaction was monitored by GC analysis and was found to be complete after one hour. The catalyst was filtered and the filtrate was concentrated to afford an off-white crystalline product. The crude product was dissolved in hot acetonitrile (1.2 L), and then filtered while hot. The filtrate was diluted with ethyl acetate (1.2 L). The clear solution was allowed to stand overnight at room temperature. The first crop of crystals was collected and dried under vacuum to afford 52 g of sub-title compound as a white solid. The filtrate was concentrated to near dryness, then dissolved in hot acetonitrile (0.4 L), and diluted with ethyl acetate (0.4 L). A second crop of crystals (38 g) was obtained after cooling the solution to 10° C. Both crops were found to be comparable by GC analysis and 1H NMR analyses. Combined yield: 90 g (83%).

Workup

  1. filtrationThe catalyst was filtered
  2. concentrationthe filtrate was concentrated
  3. customto afford an off-white crystalline product
  4. filtrationfiltered while hot
  5. additionThe filtrate was diluted with ethyl acetate (1.2 L)
  6. waitto stand overnight at room temperature
  7. customThe first crop of crystals was collected
  8. customdried under vacuum

Sources & evidence

ORD record
ord-1dc10b415f4841888919ce896e02982b
Source dataset
uspto-grants-2007_05
Patent number
US07217708B2

Reaction notes

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