Methyl chloroformate → 1-Tert-butyl 4,4-dimethyl piperidine-1,4,4-tricarboxylate

HRID 525493Notes

Reaction equation

HRID 525493 reaction equation
[N:1]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.[C:26](Cl)(=[O:29])[O:27][CH3:28].[NH4+].[Cl-]>C1COCC1>[N:1]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:2][CH2:3][C:4]([C:26]([O:27][CH3:28])=[O:29])([C:7]([O:9][CH3:10])=[O:8])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 25517Ammonium ChlorideHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 2724682Lithium diisopropylamide

Product 1

HCID 579202841-Tert-butyl 4,4-dimethyl piperidine-1,4,4-tricarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (1.3 g, 5.35 mmol, 1.0 eq) in dry THF (35 mL) was added LDA (2N, 3.25 mL, 6.42 mmol, 1.2 eq) dropwise at −78° C. under N2. Then the mixture was stirred at −78° C. for 1 h. Then methyl carbonochloridate (0.55 g, 5.89 mmol, 1.1 eq) was added dropwise to this mixture. The resulting mixture was warmed to rt slowly for 4 h. Saturated NH4Cl solution was added to this mixture, extracted with EtOAc (75 mL×2), washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give 1-tert-butyl 4,4-dimethyl piperidine-1,4,4-tricarboxylate as yellow oil (1.25 g, Y: 78%).

Workup

  1. temperatureThe resulting mixture was warmed to rt slowly for 4 h
  2. extractionextracted with EtOAc (75 mL×2)
  3. washwashed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-92cbc7a833104aaf9caa2be092a4a7f1
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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