Methanol → N-Cbz-4,4'-bipiperidine

HRID 2171677Notes

Reaction equation

HRID 2171677 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH2:5][CH2:4]1.CO.Cl[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].[OH-].[Na+]>C1(C)C=CC=CC=1>[N:3]1([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:8][CH2:7][CH:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 887MethanolHCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 122706374,4'-Bipiperidine dihydrochloride

Product 1

HCID 10979576N-Cbz-4,4'-bipiperidineYield 40.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4,4′-Bipiperidine dihydrochloride (2.95 g) was mixed with MeOH (25 ml), and a mixture of benzyl chloroformate (2.2 g) and toluene (5 ml) was added dropwise thereto over 1 hour while keeping the solution neutral by adding a 6M aqueous NaOH solution at the same time. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. CHCl3, and a saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain benzyl 4,4′-bipiperidine-1-carboxylate (1.5 g).

Workup

  1. additionwas added dropwise
  2. concentrationconcentrated under reduced pressure
  3. additionCHCl3, and a saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-d056defc71eb44588730f0a6430581fb
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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