Cyclohexanol → 2-Fluoro-4-[4-(methoxymethylidene)cyclohexyl]benzonitrile

HRID 2231805Notes

Reaction equation

HRID 2231805 reaction equation
[K].CCSC([N:7]([CH2:12][CH:13]([CH3:15])[CH3:14])CC(C)C)=O.[Cl-].C1([C:23]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)(C2C=CC=CC=2)[O:24][CH2:25][PH3+])C=CC=CC=1.[C:39]([C:41]1C=CC(C2CCC(=O)CC2)=C[C:42]=1F)#N.BrC1C=CC(C#N)=C([F:64])C=1.C1OC2(CCC(=O)CC2)OC1.C([Li])CCC.C1(O)CCCCC1>C(OC(C)C)(C)C.CCOCC.C1COCC1.O>[CH3:25][O:24][CH:23]=[C:33]1[CH2:34][CH2:35][CH:36]([C:41]2[CH:42]=[CH:14][C:13]([C:12]#[N:7])=[C:15]([F:64])[CH:39]=2)[CH2:37][CH2:38]1

Participants

13

Reactant 8

HCID 7966CyclohexanolHCID 16181ButylateHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 7360294-Bromo-2-fluorobenzonitrileHCID 5462222PotassiumHCID 137104062-Fluoro-4-(4-oxocyclohexyl)benzonitrileHCID 22385972Trityloxymethylphosphanium chlorideHCID 178418339Butyllithium

Product 1

HCID 137104072-Fluoro-4-[4-(methoxymethylidene)cyclohexyl]benzonitrile

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 7914Diisopropyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.8 g of solid potassium t.-butylate are added at -15° to a suspension of 5.3 g of triphenylmethoxymethylphosphonium chloride in 100 ml of diisopropyl ether, and the mixture is stirred for a further 30 minutes. A solution of 2.3 g of 4-(4-cyano-3-fluorophenyl)-cyclohexanone [obtainable by reacting 4-bromo-2-fluorobenzonitrile and cyclohexane-1,4-dione monoethylene ketal with butyllithium in ether at -100° by the method of W. E. Porham and L. D. Jones, J. Org. Chem. 41, 1187, 2704 (1976), subsequently eliminating water from the resulting cyclohexanol, hydrogenating the double bond and splitting off the ethylene ketal protective group] in 30 ml of THF is then added dropwise to the suspension, and the reaction mixture is stirred for a further 3 hours at room temperature, then poured into 300 ml of petroleum ether and filtered. Working up the filtrate in the customary manner gives 4-[4-(methoxymethylene)cyclohexyl]-2-fluorobenzonitrile as a colourless oil. A mixture of 1.0 g of this oil, 20 ml of THF and 5 ml of 2N hydrochloric acid is boiled for 30 minutes and then worked up in the customary manner. Trans-4-(4-cyano-3-fluorophenyl)-cyclohexanecarbaldehyde is obtained after crystallisation.

Workup

  1. customat -100°
  2. additionis then added dropwise to the suspension
  3. stirringthe reaction mixture is stirred for a further 3 hours at room temperature
  4. filtrationfiltered

Sources & evidence

ORD record
ord-2c03a3cd68624cba932a8b69c2bd4766
Source dataset
uspto-grants-1988_11
Patent number
US04784471

Reaction notes

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