Methyl iodide → 1-(tert-Butoxycarbonyl)-2-methylpiperidine-2-carboxylic acid

HRID 1644797Notes

Reaction equation

HRID 1644797 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]1[C:22]([OH:24])=[O:23])=[O:15])([CH3:12])([CH3:11])[CH3:10].CI>C1COCC1.CCCCCCC.C1COCC1>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C:17]1([CH3:2])[C:22]([OH:24])=[O:23])=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 5818311-[(Tert-butoxy)carbonyl]piperidine-2-carboxylic acidHCID 2724682Lithium diisopropylamide

Product 1

HCID 426147871-(tert-Butoxycarbonyl)-2-methylpiperidine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21263495Tetrahydrofuran heptaneSolvent

Procedure

To a solution of LDA (9.6 mL of a 2M solution in THF/Heptane) in THF (15 mL) at 0° C. was added 1-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid (2 g as a suspension in 4 mL of THF) dropwise via syringe over 10 minutes. The reaction mixture was stirred a further 20 minutes and then MeI (1.238 g) was added in one portion via syringe. The reaction mixture was allowed to warm to RT and stirred for 72 hours. The reaction was quenched with 2N aqueous HCl solution and diluted with EtOAc. The phases were separated and the aqueous phase was extracted with further EtOAc. The combined organics were washed with brine and dried over sodium sulfate. Filtration and evacuation of the volatiles in vacuo afforded a crude residue which was purified by flash column chromatography over silica gel (Heptane/EtOAc) to afford the desired (rac)-2-methyl-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (810 mg, MS (ES−): 242.4 (M−H), brown crystals).

Workup

  1. stirringstirred for 72 hours
  2. customThe reaction was quenched with 2N aqueous HCl solution
  3. additiondiluted with EtOAc
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with further EtOAc
  6. washThe combined organics were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationFiltration and evacuation of the volatiles in vacuo
  9. customafforded a crude residue which
  10. customwas purified by flash column chromatography over silica gel (Heptane/EtOAc)

Sources & evidence

ORD record
ord-32c84c10500d430499f02ed57847b4a5
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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