1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1,1-Dimethylethyl 4-[({[2-(trifluoromethyl)phenyl]methyl}amino)-carbonyl]-1-piperidinecarboxylate

HRID 1678415

Reaction equation

HRID 1678415 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].[F:17][C:18]([F:28])([F:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][NH2:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C>[F:17][C:18]([F:27])([F:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][NH:26][C:14]([CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:16]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 764472-(Trifluoromethyl)benzylamineHCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 673389391,1-Dimethylethyl 4-[({[2-(trifluoromethyl)phenyl]methyl}amino)-carbonyl]-1-piperidinecarboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a suspension of 1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinecarboxylic acid (8.00 g, 34.9 mmol, 1.00 equiv) in CH2Cl2/DMF (7/1, 350 ml) at room temperature, 1-[2-(trifluoromethyl)phenyl]methanamine (4.90 mL, 34.9 mmol, 1.00 equiv), EDCI (8.03 g, 41.9 mmol, 1.20 equiv), HOBT (5.66 g, 41.9 mmol, 1.20 equiv), and diisopropylethylamine (DIEA, 18.3 ml, 105 mmol, 3.00 equiv) were added. Stirring was continued overnight at room temperature. The reaction mixture was partitioned between water and ethyl acetate (1:1, 600 ml). The product was extracted three times with ethyl acetate (100 ml). The organic extracts were combined and washed successively with saturated ammonium chloride (200 ml), water (200 ml), and saturated sodium chloride (200 ml). The ethyl acetate solution was dried with Na2SO4, filtered, and concentrated under reduced pressure to afford 11.67 g (87%) of the title compound. MS (ES+): m/e 408.9 [M+Na]+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate (1:1, 600 ml)
  2. extractionThe product was extracted three times with ethyl acetate (100 ml)
  3. washwashed successively with saturated ammonium chloride (200 ml), water (200 ml), and saturated sodium chloride (200 ml)
  4. dry with materialThe ethyl acetate solution was dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d449caa4f62442c881ea5d5ab9481a58
Source dataset
uspto-grants-2011_08
Patent number
US08008483B2

Linked notes

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