Diisopropylethylamine → 5-Oxo-5-(3-phenoxyazetidin-1-yl)-2,2-diphenylpentanenitrile

HRID 2387667Notes

Reaction equation

HRID 2387667 reaction equation
[C:1]([C:3]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:4][CH2:5][C:6]([OH:8])=O)#[N:2].Cl.CN(C)CCCN=[C:28]=[N:29][CH2:30][CH3:31].[OH2:33].ON1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl.C(OCC)(=O)C>[O:8]=[C:6]([N:29]1[CH2:28][CH:31]([O:33][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:30]1)[CH2:5][CH2:4][C:3]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:1]#[N:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 537742904-Cyano-4,4-diphenylbutanoic acid

Product 1

HCID 674383535-Oxo-5-(3-phenoxyazetidin-1-yl)-2,2-diphenylpentanenitrileYield 75%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of the product of preparation 64 (1.13 g, 7.6 mmol), 4-cyano-4,4-diphenylbutanoic acid [(2.4 g, 9.12 mmol), WO97/24325], 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.76 g, 9.12 mmol), 1-hydroxybenzotriazole hydrate (1.30 g, 9.12 mmol) and N,N-diisopropylethylamine (5.3 mL, 19 mmol) in dichloromethane (50 mL) was stirred at room temperature for 18 hours. The reaction mixture was then diluted with ethyl acetate (50 mL), washed with 2M hydrochloric acid (30 mL), and sodium hydrogen carbonate solution (30 mL), dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with pentane:ethyl acetate, 100:0 to 0:100, then afforded the title compound as a colourless oil in 75% yield, 2.28 g.

Workup

  1. washwashed with 2M hydrochloric acid (30 mL), and sodium hydrogen carbonate solution (30 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by column chromatography on silica gel
  5. washeluting with pentane

Sources & evidence

ORD record
ord-2d429e65997d4ad68527f16169235099
Source dataset
uspto-grants-2012_09
Patent number
US08268881B2

Reaction notes

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