Triethylamine → 1-(4-Aminophenyl)cyclopropanecarbonitrile
Reaction equation
[C:1]([C:3]1([C:6]2[CH:14]=[CH:13][C:9](C(O)=O)=[CH:8][CH:7]=2)[CH2:5][CH2:4]1)#[N:2].C1(P([N:29]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>C(O)(C)(C)C>[NH2:29][C:9]1[CH:13]=[CH:14][C:6]([C:3]2([C:1]#[N:2])[CH2:5][CH2:4]2)=[CH:7][CH:8]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
750 mg (4 mmol) of 4-(1-cyano-cyclopropyl)-benzoic acid (Example 110b) in 20 ml of tert-butanol are stirred in presence of 0.86 ml (4 mmol) diphenylphosphoryl azide (DPPA, Fluka, Buchs, Switzerland) and 0.59 ml (4 mmol) triethylamine at 95° C. for 3 h. Are added 0.43 ml (2 mmol) DPPA and 0.29 ml (2 mmol) triethylamine and the reaction mixture is stirred at 95° C. for 30 min. The reaction mixture is evaporated to dryness and then is taken in EtOAc and washed with H2O, dried over Na2SO4, filtered and evaporated. The solid is separated by flash chromatography (CH2Cl2-MeOH 99:1). The purified compound is treated in 5 ml 4 M HCl in dioxane at rt for 2 h. The crude deprotected product is purified by flash chromatography (CH2Cl2-MeOH 98:2). The product is triturated in MeOH to give the title compound. Analytical HPLC: tret=3.68 minutes (Grad 2).
Workup
- customThe reaction mixture is evaporated to dryness
- washwashed with H2O
- dry with materialdried over Na2SO4
- filtrationfiltered
- customevaporated
- customThe solid is separated by flash chromatography (CH2Cl2-MeOH 99:1)
- additionThe purified compound is treated in 5 ml 4 M HCl in dioxane at rt for 2 h
- customThe crude deprotected product is purified by flash chromatography (CH2Cl2-MeOH 98:2)
- customThe product is triturated in MeOH
Sources & evidence
- ORD record
- ord-bcaa43a057db4230a0ca59c0455bb0c6
- Source dataset
- uspto-grants-2010_02
- Patent number
- US07667039B2
Reaction notes
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