2,5-Dioxopyrrolidin-1-yl (4-methylbenzyl) carbonate → cis 3-Hydroxy-4-(pyridin-4-ylaminomethyl)-piperidine-1-carboxylic acid 4-methyl-benzyl ester

HRID 1827135Notes

Reaction equation

HRID 1827135 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][CH2:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH:10]2[OH:15])=[CH:3][CH:2]=1.[CH3:16][C:17]1[CH:34]=[CH:33][C:20]([CH2:21][O:22][C:23](=O)[O:24]N2C(=O)CCC2=O)=[CH:19][CH:18]=1>CN(C=O)C>[CH3:16][C:17]1[CH:34]=[CH:33][C:20]([CH2:21][O:22][C:23]([N:12]2[CH2:13][CH2:14][C@H:9]([CH2:8][NH:7][C:4]3[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=3)[C@H:10]([OH:15])[CH2:11]2)=[O:24])=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 111399512,5-Dioxopyrrolidin-1-yl (4-methylbenzyl) carbonate2×HCID 221356624-(Pyridin-4-ylaminomethyl)-piperidin-3-ol

Product 1

HCID 58635347cis 3-Hydroxy-4-(pyridin-4-ylaminomethyl)-piperidine-1-carboxylic acid 4-methyl-benzyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of the 4-(pyridin-4-ylaminomethyl)-piperidin-3-ol from Step 2 above (0.076 g, 0.367 mmol) in DMF (1.5 mL) was treated with carbonic acid 2,5-dioxo-pyrrolidin-1-yl ester 4-methyl-benzyl ester (0.097 g, 0.37 mmol) (INTERMEDIATE 1A) and the resulting reaction mixture stirred at rt for 5 min. The mixture was then partitioned between dilute sodium carbonate solution and EtOAc. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and the solvent evaporated to give a crude product. Purification by flash column chromatography (DCM to 80/20/2 DCM MeOH NH4OH) afforded the cis 3-hydroxy-4-(pyridin-4-ylaminomethyl)-piperidine-1-carboxylic acid 4-methyl-benzyl ester compound. M.S (M+1): 356.

Workup

  1. customthe resulting reaction mixture
  2. customThe mixture was then partitioned between dilute sodium carbonate solution and EtOAc
  3. washThe organic layer was washed with saturated sodium bicarbonate solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent evaporated
  6. customto give a crude product
  7. customPurification by flash column chromatography (DCM to 80/20/2 DCM MeOH NH4OH)

Sources & evidence

ORD record
ord-17560bc33ae54f298ac0b6cbd351865d
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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