Cyclohexanone → Tert-butyl 8-cyclohexyl-2,8-diazaspiro[4.5]decane-2-carboxylate

HRID 1916374Notes

Reaction equation

HRID 1916374 reaction equation
Cl.[CH2:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][N:3]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[C:19]1(=O)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.[Na].[OH-].[Na+]>O.C(O)(=O)C>[CH:19]1([N:9]2[CH2:8][CH2:7][C:6]3([CH2:2][N:3]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:4][CH2:5]3)[CH2:11][CH2:10]2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 7967CyclohexanoneHCID 14798Sodium HydroxideHCID 5360545SodiumHCID 666620882-Boc-2,8-Diazaspiro[4.5]decane hydrochloride

Product 1

HCID 68969463Tert-butyl 8-cyclohexyl-2,8-diazaspiro[4.5]decane-2-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Under an argon atmosphere, tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate hydrochloride (3.2 g) and a 10% acetic acid-anhydrous N,N-dimethylformamide (50 mL) solution of cyclohexanone (1.9 mL) were stirred at room temperature for 4 hours. To the resultant solution, sodium tiacetoxy borohydride (5.2 g) was added. The reaction solution was stirred at room temperature for 15 hours. To the reaction solution, water (100 mL) and an aqueous 1N-sodium hydroxide solution (100 mL) were added. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated saline and then dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was removed by filtration and the solvent was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate:methanol=1:0→8:2) to obtain the title compound having the following physical properties (3.7 g).

Workup

  1. extractionThe aqueous layer was extracted twice with ethyl acetate
  2. washwashed with saturated saline
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe anhydrous sodium sulfate was removed by filtration
  5. concentrationthe solvent was concentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (ethyl acetate:methanol=1:0→8:2)

Sources & evidence

ORD record
ord-803a1936374348039bb2792773e231f9
Source dataset
uspto-grants-2013_12
Patent number
US08618122B2

Reaction notes

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