Ethyl 4-piperidinecarboxylate → 1-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid

HRID 910458Notes

Reaction equation

HRID 910458 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2([CH3:17])[CH2:16][CH2:15]2)=[O:13])[CH2:8][CH2:7]1)=[O:5])C.C(OC(C1CCNCC1)=O)C.CC1(C(O)=O)CC1.O[Li].O>C1COCC1.CCO.O>[CH3:17][C:14]1([C:12]([N:9]2[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]2)=[O:13])[CH2:15][CH2:16]1

Participants

8

Reactant 4

HCID 70770Ethyl 4-piperidinecarboxylateHCID 813261-Methylcyclopropanecarboxylic acidHCID 168937Lithium hydroxide, monohydrateHCID 594381441-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester2×

Product 1

HCID 594381681-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acidYield 86.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

First step: Using the general procedure I for the preparation of amide, 2.60 g of 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester was prepared from 1.89 g of piperidine-4-carboxylic acid ethyl ester and 1.40 g of 1-methyl-cyclopropanecarboxylic acid as a light yellow oil. ES-MS m/e: 240.3 (M+H+). Second step: To a stirred solution of 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester (2.60 g, 0.011 mmol) in THF, EtOH, H2O (50 ml, 1/1/1) was added LiOH.H2O (686 mg, 16.3 mmol). After two hours at RT, the reaction mixture was concentrated under vacuo. The crude residue was diluted in CH2Cl2 and aqueous HCl (1N) was added until pH=2. The organic phase was collected, dried over Na2SO4 and concentrated under vacuo to afforded 1.98 g (86%) of the title product as a white powder. ES-MS m/e: 212.1 (M+H+).

Workup

  1. concentrationthe reaction mixture was concentrated under vacuo
  2. additionThe crude residue was diluted in CH2Cl2
  3. additionaqueous HCl (1N) was added until pH=2
  4. customThe organic phase was collected
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-525cdaad03984ff49e716ecb42d477f7
Source dataset
uspto-grants-2011_09
Patent number
US08022099B2

Reaction notes

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