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

HRID 905853Notes

Reaction equation

HRID 905853 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 (100 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-f51828a6b95541ac94962b0ff01954c2
Source dataset
uspto-grants-2011_09
Patent number
US08012966B2

Reaction notes

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