Ethyl butyrate → 5-[(2'-Cyanobiphenyl-4-yl)methyl]-4,6-dioxononane

HRID 274252

Reaction equation

HRID 274252 reaction equation
[O:1]=[C:2]([CH2:6][C:7](=[O:11])[CH2:8][CH2:9][CH3:10])[CH2:3][CH2:4][CH3:5].C(C(C)=O)CC.C(OCC)(=O)CCC.[NH2-].[Li+].[H-].[Na+].Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:44]#[N:45])=[CH:34][CH:33]=1>CN(C=O)C>[C:44]([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=1[C:35]1[CH:34]=[CH:33][C:32]([CH2:31][CH:6]([C:7](=[O:11])[CH2:8][CH2:9][CH3:10])[C:2](=[O:1])[CH2:3][CH2:4][CH3:5])=[CH:37][CH:36]=1)#[N:45]

Participants

8

Reactant 6

HCID 7762Ethyl butyrateHCID 78952-PentanoneHCID 24532Lithium amideHCID 24758Sodium hydrideHCID 264544,6-NonanedioneHCID 15019124'-(Bromomethyl)-2-cyanobiphenyl

Product 1

HCID 200928635-[(2'-Cyanobiphenyl-4-yl)methyl]-4,6-dioxononaneYield 104.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

15.6 g of 4,6-dioxononane, prepared from methyl propyl ketone and ethyl butyrate in the presence of lithium amide (according to CA 42 : 4129 f), are dissolved in 160 ml of anhydrous DMF. 4 g of 60% NaH are added in portions. When the exothermic effect has subsided, the mixture is cooled to room temperature and a solution of 27.2 g of 4'-bromomethyl-2-cyanobiphenyl, prepared in Example 4, in 90 ml of DMF is introduced dropwise. The mixture is stirred for 30 min at room temperature and then heated at 60° C. for 2 h. It is concentrated under vacuum and the concentrate is taken up in a water/dichloromethane mixture and acidified with a dilute solution of HCl. After decantation, the aqueous phase is extracted twice with dichloromethane. The organic phases are washed with water, dried and then concentrated to give 36.3 g of an oil, which is purified by chromatography twice in succession (eluent: chloroform, then cyclohexane 90%/ethyl acetate 10% respectively) to give a solid identified by NMR as being the enol tautomer melting at 105° C., and an oil corresponding to the diketone tautomeric form.

Workup

  1. additionis introduced dropwise
  2. temperatureheated at 60° C. for 2 h
  3. concentrationIt is concentrated under vacuum
  4. extractionAfter decantation, the aqueous phase is extracted twice with dichloromethane
  5. washThe organic phases are washed with water
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-93a37d520490420fbbdb674b463811c7
Source dataset
uspto-grants-1995_02
Patent number
US05389632

Linked notes

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