4-Chloropyridine → cis 3-Hydroxy-4-(pyridin-4-ylaminomethyl)-piperidine-1-carboxylic acid benzyl ester

HRID 1351495Notes

Reaction equation

HRID 1351495 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@H:14]([CH2:17][NH2:18])[C@H:13]([OH:19])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>C(O)(C)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@H:14]([CH2:17][NH:18][C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)[C@H:13]([OH:19])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 122884-ChloropyridineHCID 58635348(cis)-4-Aminomethyl-3-hydroxy-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 58635330cis 3-Hydroxy-4-(pyridin-4-ylaminomethyl)-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of the cis 4-aminomethyl-3-hydroxy-piperidine-1-carboxylic acid benzyl ester (245 mg) from Step 4 above, 4-chloropyridine (105 mg) and isopropanol (0.4 mL) was heated to 120° C. in a sealed vial for 24 h, cooled to room temperature and the solvents evaporated. The resulting crude mixture was purified by flash column chromatography (DCM to 80/20/2 DCM MeOH NH4OH) to give impure cis 3-hydroxy-4-(pyridin-4-ylaminomethyl)-piperidine-1-carboxylic acid benzyl ester. This was purified by preparative reverse phase HPLC (95% H2O 5% MeCN to 100% MeCN both containing 0.1% TFA). Evaporation gave an oil which was partitioned between DCM and aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and solvent evaporated to give a white solid. M.S (M+1): 342.

Workup

  1. customthe solvents evaporated
  2. customThe resulting crude mixture was purified by flash column chromatography (DCM to 80/20/2 DCM MeOH NH4OH)

Sources & evidence

ORD record
ord-83122873122b4410854ac7ee2f0c97ab
Source dataset
uspto-grants-2007_05
Patent number
US07217716B2

Reaction notes

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