Hexamethylphosphoramide → 2-(Benzhydrylideneamino)-3-quinolin-4-yl-butyronitrile
Reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][CH2:9][C:10]#[N:11])=[CH:3][CH:2]=1.CN(P(N(C)C)(N(C)C)=O)C.[Li+].CC([N-]C(C)C)C.Cl[CH:38]([C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:43]=[CH:42][CH:41]=1)[CH3:39]>C1COCC1>[C:7](=[N:8][CH:9]([CH:38]([C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:43]=[CH:42][CH:41]=1)[CH3:39])[C:10]#[N:11])([C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To N-(Diphenylmethylene)aminoacetonitrile (2.26 g, 10.2 mmol) in 10 ml of anhydrous THF and HMPA (2.17 ml, 12.14 mmol), at −78° C. LDA (2.0 M, 6.0 ml, 12.14 mmol) was added dropwise over a period of 5 minutes. The color of solution turns from coloress to yellow to dark brown. It was then stirred at −78° C. for one hour. Then 4-(1-Chloroethyl)-quinoline (1.79 g, 9.34 mmol), was added dropwise and the reaction mixture was slowly brought to room temperature over a period of five minutes, quenched by addition of ice and partitioned between EtOAc (20 ml) and water (5 ml). The organic layer was dried over sodium sulfate, filtered, concentrated and column purified (hexanes:EtOAc; 3.5:1.5) to give 3.0 g (86%) of the product as a syrup which was used as such for the subsequent step.
Workup
- customat −78° C
- waitthe reaction mixture was slowly brought to room temperature over a period of five minutes
- customquenched by addition of ice
- custompartitioned between EtOAc (20 ml) and water (5 ml)
- dry with materialThe organic layer was dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customcolumn purified (hexanes:EtOAc; 3.5:1.5)
Sources & evidence
- ORD record
- ord-3b8dfc750974401f910f454705b8ccdc
- Source dataset
- uspto-grants-2001_09
- Patent number
- US06294566B1
Reaction notes
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