4-Methylmorpholine → 3-Hydroxy-4-[(2,3,5,6-tetrachloro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester

HRID 1827133Notes

Reaction equation

HRID 1827133 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N+:9]([O-])=O)[C:5]([Cl:12])=[C:4]([Cl:13])[N:3]=1.[CH2:14]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C@H:27]([CH2:30]N)[C@H:26]([OH:32])[CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN1CCOCC1>C1COCC1>[CH2:14]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([CH2:30][NH:9][C:6]2[C:7]([Cl:8])=[C:2]([Cl:1])[N:3]=[C:4]([Cl:13])[C:5]=2[Cl:12])[CH:26]([OH:32])[CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 152291672,3,5,6-Tetrachloro-4-nitropyridineHCID 58635348(cis)-4-Aminomethyl-3-hydroxy-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 235772743-Hydroxy-4-[(2,3,5,6-tetrachloro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,3,5,6-tetrachloro-4-nitropyridine (S. M. Roberts et al., J. Chem. Soc. C, 2844–2848(1968)) (1.7 g, 6.5 mmol) was added to a solution of (cis)-4-aminomethyl-3-hydroxy-piperidine-1-carboxylic acid benzyl ester (1.71 g, 6.49 mmol) and N-methylmorpholine (0.785 mL, 7.15 mmol) in THF (50 mL) at room temperature. The resulting reaction mixture was stirred for 18 h at room temperature then partitioned between EtOAc and water. The organic layer was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and the solvent evaporated to give crude product purified by flash column chromatography (20–80% EtOAc hexane) to give 3-hydroxy-4-[(2,3,5,6-tetrachloro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester compound. M.S (M+1): 478.

Workup

  1. customThe resulting reaction mixture
  2. customthen partitioned between EtOAc and water
  3. washThe organic layer was washed with saturated sodium bicarbonate solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent evaporated
  6. customto give crude product
  7. custompurified by flash column chromatography (20–80% EtOAc hexane)

Sources & evidence

ORD record
ord-0049026c33054e4ba3b24ec11ca1a8b3
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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