2,4-Dichloropyrimidine → (R)-1-(2-Chloropyrimidin-4-YL)piperidine-3-carboxylic acid

HRID 1019651Notes

Reaction equation

HRID 1019651 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]([C:15]([OH:17])=[O:16])[CH2:10]1>CCO>[Cl:1][C:2]1[N:7]=[C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([C:15]([OH:17])=[O:16])[CH2:10]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 775312,4-DichloropyrimidineHCID 1796510(-)-Nipecotic acid

Product 1

HCID 52319915(R)-1-(2-Chloropyrimidin-4-YL)piperidine-3-carboxylic acidYield 21%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2,4-dichloropyrimidine (2.307, 15.49 mmol) and TEA (2.15 mL, 15.49 mmol) in EtOH (19.36 mL) at −10° C. was added (R)-piperidine-3-carboxylic acid (Sigma Aldrich, 2 g, 15.49 mmol). The reaction was allowed to slowly warm to room temperature while stirring. After 20 hours, the reaction was concentrated. The residue was adsorbed onto a plug of silica gel and purified by chromatography through a 100 g silica gel column, eluting with 2% to 10% MeOH in DCM followed by 20% to 50% 5:45:50 folic acid:EtOH:DCM, to provide M4.1 as a white solid in 21% yield. 1H NMR (400 MHz, CD3OD) δ ppm 1.51-1.63 (m, 1H) 1.76-1.91 (m, 2H) 2.09 (dd, J=8.71, 4.40 Hz, 1H) 2.51-2.60 (m, 1H) 3.33-3.51 (m, 3H) 4.01 (br. s., 1H) 6.74 (d, J=6.46 Hz, 1H) 7.96 (d, J=6.26 Hz, 1H); ESI-MS M+H 241.9.

Workup

  1. concentrationthe reaction was concentrated
  2. custompurified by chromatography through a 100 g silica gel column
  3. washeluting with 2% to 10% MeOH in DCM
  4. customEtOH:DCM, to provide M4.1 as a white solid in 21% yield

Sources & evidence

ORD record
ord-3487cf6ac8c24cb6a7f65bb59af1b0a1
Source dataset
uspto-grants-2014_05
Patent number
US08716281B2

Reaction notes

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