1,1'-Carbonyldiimidazole → 1-(1-Trifluoromethyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester

HRID 222592Notes

Reaction equation

HRID 222592 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[F:13][C:14]([F:22])([F:21])[C:15]1([C:18](O)=[O:19])[CH2:17][CH2:16]1.[CH2:23]([O:25][C:26]([CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)=[O:27])[CH3:24]>O1CCCC1>[CH2:23]([O:25][C:26]([CH:28]1[CH2:33][CH2:32][N:31]([C:18]([C:15]2([C:14]([F:22])([F:21])[F:13])[CH2:17][CH2:16]2)=[O:19])[CH2:30][CH2:29]1)=[O:27])[CH3:24]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 70770Ethyl 4-piperidinecarboxylateHCID 27783061-(Trifluoromethyl)cyclopropane-1-carboxylic acid

Product 1

HCID 668652731-(1-Trifluoromethyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl esterYield 102.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1′-Carbonyldiimidazole (77.36 g; 467.52 mmol) is added to a solution of 1-(trifluoromethyl)cyclopropanecarboxylic acid (72.04 g; 467.52 mmol) in tetrahydrofuran (600 mL) while keeping the internal temperature below 30° C. Piperidine-4-carboxylic acid ethyl ester (50 g; 311.68 mmol) is added after 10 min and the reaction is stirred under nitrogen atmosphere at room temperature for 16 h. The solvent is removed under controlled vacuum and the residue is partitioned between 2 M aqueous solution of sodium hydroxide (200 mL) and dichloromethane (300 mL). The organic layer is washed with brine (100 mL), dried over magnesium sulphate, filtered and concentrated to obtain 93.45 g of the title compound. MS (m/z) 294 (M+1).

Workup

  1. customthe internal temperature below 30° C
  2. customThe solvent is removed under controlled vacuum
  3. customthe residue is partitioned between 2 M aqueous solution of sodium hydroxide (200 mL) and dichloromethane (300 mL)
  4. washThe organic layer is washed with brine (100 mL)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7b121c550df14e8fa59c5e078c988145
Source dataset
uspto-grants-2012_06
Patent number
US08207344B2

Reaction notes

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