Di-tert-butyl dicarbonate → tert-butyl (3S)-3-hydroxypiperidine-1-carboxylate

HRID 1726365Notes

Reaction equation

HRID 1726365 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>ClCCl.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 5456991-Boc-3-hydroxypiperidine

Product 1

HCID 1514399tert-butyl (3S)-3-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

3-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester. To a mixture of sodium bicarbonate (403.3 g, 4.8 mol) and water (1.6 L) was added (S)-3-hydroxypiperidine (R)-1-(−)-camphor-10-sulfonic acid salt (3, 400.14 g, 1.2 mol) and dichloromethane (1.6 L). The mixture was stirred for 30 minutes and cooled by ice bath. To the mixture was added di-tert-butyl dicarbonate (288.1 g, 1.32 mol) portionwise in 30 minutes. The mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane (4.8 L) and H2O (4.8 L) and separated in separation funnel. The organic layer was washed with brine (2 L), dried (Na2SO4) and concentrated to give the desired product (S)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester in quantitative yield (241.5 g).

Workup

  1. temperaturecooled by ice bath
  2. stirringThe mixture was stirred at room temperature overnight
  3. customseparated in separation funnel
  4. washThe organic layer was washed with brine (2 L)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-942c4447a7994021a5688b7d3bd00ce9
Source dataset
uspto-grants-2009_02
Patent number
US07491826B2

Reaction notes

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