1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-(2-Phenyl-piperidine-1-carbonyl)-piperidine-1-carboxlic acid tert.-butyl ester

HRID 2362773Notes

Reaction equation

HRID 2362773 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]1([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][NH:24]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(Cl)Cl.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([N:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH:23]2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:16])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1030202-PhenylpiperidineHCID 27356471-((Tert-butoxy)carbonyl)piperidine-3-carboxylic acid

Product 1

HCID 578223103-(2-Phenyl-piperidine-1-carbonyl)-piperidine-1-carboxlic acid tert.-butyl esterYield 31.1%

Reagents, catalysts & solvents 2

HCID 22350042dichloromethane N,N-dimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 2 g of 1-(tert-butoxycarbonyl)-3-piperidinecarboxylic acid (commercially available) (8.72 mmol) in 15 mL of DMF:DCM (3:1) was added 1.39 g 2-phenylpiperidine (commercially available) (8.72 mmol) and 3.04 mL DIPEA (17.4 mmol). The mixture was stirred at room temperature for 10 minutes. 2.5 g EDCI (13.1 mmol) and 2.04 g HOBT (13.1 mmol) was added. The mixture was stirred for 6 h at room temperature, diluted with brine (50 mL) and extracted with ethyl acetate (2×40 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated at reduced pressure to obtain the crude product, which was further purified by column chromatography on silica eluting with 30-35% ethyl acetate in hexane to yield 1 g (31%) of the title compound. (MH+) 372.18.

Workup

  1. stirringThe mixture was stirred for 6 h at room temperature
  2. extractionextracted with ethyl acetate (2×40 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated at reduced pressure
  6. customto obtain the crude product, which
  7. customwas further purified by column chromatography on silica eluting with 30-35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-7c117a5dec7c4b098e683f6c0ceea7de
Source dataset
uspto-grants-2014_04
Patent number
US08691846B2

Reaction notes

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