1-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylate → rac-tert-Butyl 1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonane-6-carboxylate

HRID 1036731Notes

Reaction equation

HRID 1036731 reaction equation
[Li+].CC([N-]C(C)C)C.C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C.[N:29]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:34][CH2:33][CH2:32][CH:31]([C:35]([O:37]CC)=O)[CH2:30]1.[CH:47](=[N:54][Si](C)(C)C)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C1COCC1>[O:37]=[C:35]1[C:31]2([CH2:32][CH2:33][CH2:34][N:29]([C:40]([O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:41])[CH2:30]2)[CH:47]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[NH:54]1

Participants

6

Reactant 4

HCID 3577271-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylateHCID 595493N-TrimethylsilylbenzaldimineHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 71060527rac-tert-Butyl 1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonane-6-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2M LDA in THF/n-heptane/ethylbenzene (10.7 ml, 21.37 mmol) was cooled to −78° C. and a solution of 1-tert-butyl 3-ethyl piperidine-1,3-dicarboxylate (5 g, 19.43 mmol) in THF (5 mL) was added dropwise. The mixture was stirred for 40 minutes and allowed to warm to 0° C. for 10 minutes and cooled again to −78° C. N-benzylidene-1,1,1-trimethylsilanamine (2.63 ml, 21.37 mmol) was added and the mixture was left to stir for 3 h at 0° C. The reaction was quenched with water (5 ml) and the resulting solution was extracted using ethyl acetate. The organic portion was separated, dried (MgSO4) and concentrated in vacuo to yield a yellow oil. Purification by flash chromatography on silica (220 g column) eluting with 20-70% EtOAc in iso-hexane afforded the title compound;

Workup

  1. temperaturecooled again to −78° C
  2. waitthe mixture was left
  3. stirringto stir for 3 h at 0° C
  4. customThe reaction was quenched with water (5 ml)
  5. extractionthe resulting solution was extracted
  6. customThe organic portion was separated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto yield a yellow oil
  10. customPurification by flash chromatography on silica (220 g column)
  11. washeluting with 20-70% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-3a5c4a2563ac46fbb3400a2c7882f963
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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