Citric Acid → (2S,5R)-5-((Benzyloxy)amino)-1-(2-trimethylsilylethoxycarbonyl)piperidine-2-carboxylic acid

HRID 711002Notes

Reaction equation

HRID 711002 reaction equation
Cl.Cl.[CH2:3]([O:10][NH:11][C@H:12]1[CH2:17][NH:16][C@H:15]([C:18]([OH:20])=[O:19])[CH2:14][CH2:13]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[OH-].[Na+].C(=O)([O-])[O-].[K+].[K+].[CH3:29][Si:30]([CH2:33][CH2:34][O:35][C:36](ON1C(=O)CCC1=O)=[O:37])([CH3:32])[CH3:31].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O.O1CCOCC1>[CH2:3]([O:10][NH:11][C@H:12]1[CH2:17][N:16]([C:36]([O:35][CH2:34][CH2:33][Si:30]([CH3:32])([CH3:31])[CH3:29])=[O:37])[C@H:15]([C:18]([OH:20])=[O:19])[CH2:14][CH2:13]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 50183862,5-Dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonateHCID 117988550(2S,5R)-5-(Benzyloxyamino)piperidine-2-carboxylic acid, dihydrochloride

Product 1

HCID 131733975(2S,5R)-5-((Benzyloxy)amino)-1-(2-trimethylsilylethoxycarbonyl)piperidine-2-carboxylic acidYield 86.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To (2S,5R)-5-(benzyloxyamino)piperidine-2-carboxylic acid, dihydrochloride (3.23 g, 10 mmol) described in Example 11 were added 1,4-dioxane (10 mL), water (15 mL) and 5M sodium hydroxide (6 mL), and stirred under ice cooling. Potassium carbonate (1.38 g), N-(trimethylsilylethyloxycarbonyloxy)succinimide (2.85 g) were added further to the mixture, and the temperature was elevated to room temperature, followed by stirring overnight. The mixture was adjusted to pH 4 with citric acid.monohydrate, and extracted with ethyl acetate (50 mL) twice. The organic layer was washed with water and saturated brine and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate/hexane=1:1→1:0) to afford 3.41 g of the title compound (yield 86%).

Workup

  1. customwas elevated to room temperature
  2. stirringby stirring overnight
  3. extractionmonohydrate, and extracted with ethyl acetate (50 mL) twice
  4. washThe organic layer was washed with water and saturated brine
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-86cb3f5f93a74ef4a2c9dd92552f2ef9
Source dataset
uspto-grants-2015_11
Patent number
US09181250B2

Reaction notes

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