Acetic Acid → (2S,5R)-tert-butyl 5-(benzyloxyamino)piperidine-2-carboxylate

HRID 925133Notes

Reaction equation

HRID 925133 reaction equation
O.[CH2:2]([O:9][NH:10][C@H:11]1[CH2:16][N:15](C(=O)C(F)(F)F)[C@H:14]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:13][CH2:12]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+].C(O)(=O)C>O1CCOCC1>[CH2:2]([O:9][NH:10][C@H:11]1[CH2:16][NH:15][C@H:14]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:13][CH2:12]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 57389515(2S,5R)-tert-Butyl 5-(benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylate

Product 1

HCID 57389512(2S,5R)-tert-butyl 5-(benzyloxyamino)piperidine-2-carboxylateYield 90.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Water (9.2 mL) was added to a solution of 6.91 g (17.17 mmol) of (2S,5R)-tert-butyl 5-(benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylate in 1,4-dioxane (34 mL), and, under ice cooling, 2.5M NaOH (13.7 mL) was added dropwise, followed by allowing to react at the same temperature for 0.5 hours. Acetic acid (ca. 1 mL) was added to the reaction mixture, followed by concentration under reduced pressure, and subsequently the resulting concentrated residue was extracted with ethyl acetate (58 mL, 29 mL). After the organic layers were washed respectively with 50% aqueous potassium carbonate solution, they were combined, followed by drying with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was applied to silica gel column chromatography (hexane/ethyl acetate=4/1→0/1→ethyl acetate/methanol=19/1) to afford 4.74 g of the title compound as a colorless oil (yield 90%). Enantiomeric excess: 98.9% ee (CHIRALPAK AD-H, 4.6×150 mm, UV 210 nm, diethylamine/hexane/ethanol=0.1/80/20, flow rate 1 mL/min., retention time 5.5 min.).

Workup

  1. customto react at the same temperature for 0.5 hours
  2. concentrationfollowed by concentration under reduced pressure
  3. extractionsubsequently the resulting concentrated residue was extracted with ethyl acetate (58 mL, 29 mL)
  4. washAfter the organic layers were washed respectively with 50% aqueous potassium carbonate solution, they
  5. dry with materialby drying with anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-324e28ccb83a495ca9a5c20c2561858a
Source dataset
uspto-grants-2016_03
Patent number
US09284273B2

Reaction notes

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