Potassium Carbonate → (RS)-4,5-Difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazole

HRID 598547Notes

Reaction equation

HRID 598547 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][C:15](O)=O)=O)(C)(C)C.[F:18][C:19]1[C:24]([F:25])=[CH:23][CH:22]=[C:21]([NH2:26])[C:20]=1[NH2:27].C(=O)([O-])[O-].[K+].[K+]>>[F:18][C:19]1[C:20]2[N:27]=[C:15]([CH2:14][CH:9]3[CH2:10][CH2:11][CH2:12][CH2:13][NH:8]3)[NH:26][C:21]=2[CH:22]=[CH:23][C:24]=1[F:25]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 27367533,4-Difluorobenzene-1,2-diamineHCID 50585361-Boc-2-Piperidineacetic Acid

Product 1

HCID 17973676(RS)-4,5-Difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazoleYield 62%

Conditions

Temperature
140 °C

Procedure

A mixture of 2-carboxymethyl-piperidine-1-carboxylic acid tert-butyl ester (Beckett et al, J. Med. Chem., 563, 1969) (6.72 g, 28 mmol) and 3,4-difluoro-benzene-1,2-diamine (4.00 g, 28 mmol) in polyphosphoric acid (130 g) was heated at 140° C. for 7.5 h. The cooled reaction mixture was poured onto excess solid potassium carbonate and crushed ice. The resulting basic, aqueous solution was extracted with ethyl acetate (2×) and the combined organics were washed with brine, dried (Na2SO4) and the solvent removed in vacuo. The residue was triturated with diethyl ether, ethyl acetate and pentane to afford the title compound as a white solid (4.29 g, 62%).

Workup

  1. customThe cooled reaction mixture
  2. customcrushed ice
  3. extractionThe resulting basic, aqueous solution was extracted with ethyl acetate (2×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customthe solvent removed in vacuo
  7. customThe residue was triturated with diethyl ether, ethyl acetate and pentane

Sources & evidence

ORD record
ord-3e465382713242fe8c5dc548afbec584
Source dataset
uspto-grants-2011_03
Patent number
US07897618B2

Reaction notes

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