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

HRID 500609Notes

Reaction equation

HRID 500609 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-30d577a8b37e40d694fe99ffbdb8a9b9
Source dataset
uspto-grants-2010_08
Patent number
US07772223B2

Reaction notes

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