Ammonia → tert-Butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate

HRID 2365116Notes

Reaction equation

HRID 2365116 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]2([O:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH3:16]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]([CH2:12][NH2:16])([OH:13])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 23396319tert-Butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylateYield 60.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred solution of 1-oxa-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (9.0 g, 42.2 mmol) in ethanol (60 ml) was added with ammonia (160 ml). The resulting mixture was stirred under a nitrogen atmosphere overnight. The mixture was concentrated under reduced pressure. The residue was added with Water (50 ml) and extracted with ethyl acetate (150 ml×3). The Combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with dichloromethane:methanol (20:1) as eluents to give 4-aminomethyl-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (5.87 g, 60.5%) as a white solid.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionThe residue was added with Water (50 ml)
  3. extractionextracted with ethyl acetate (150 ml×3)
  4. dry with materialThe Combined organic extracts were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography with dichloromethane:methanol (20:1) as eluents

Sources & evidence

ORD record
ord-2074de3a34ff48f385e455147042b7f0
Source dataset
uspto-grants-2014_04
Patent number
US08697692B2

Reaction notes

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