Piperidine → HCID 59828835, compound

HRID 1191024Notes

Reaction equation

HRID 1191024 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([CH2:16]Cl)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.C([O-])(O)=O.[Na+]>C(#N)C.O.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([CH2:16][N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 8082PiperidineHCID 516892Sodium BicarbonateHCID 59828819HCID 59828819, compound

Product 1

HCID 59828835HCID 59828835, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Add 3-(tert-butoxycarbonylamino-methyl)-6-chloromethyl-pyridine (500 mg, 1.95 mmol) to a solution of piperidine (0.58 mL, 5.84 mmol) and saturated aqueous NaHCO3 (2.5 mL) in acetonitrile (15 mL). Stir the mixture at room temperature overnight. Dilute the mixture with water (20 mL) and DCM (25 mL), separate the layers and extract the aqueous layer with DCM (3×20 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (80 g pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min) to obtain the desired intermediate as a colorless oil (547 mg, 92%). MS (APCI+) m/z: 306 (M+H)+.

Workup

  1. customseparate the layers
  2. extractionextract the aqueous layer with DCM (3×20 mL)
  3. dry with materialDry the combined organic extracts over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify by chromatography on silica gel (80 g pre-packed cartridge)
  7. washeluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min)

Sources & evidence

ORD record
ord-989185b886a14659ab65da51d00c88c4
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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