Potassium tert-butoxide → 1H-Pyrrole-3-carbonitrile, 4-(4-chlorophenyl)-5-(trifluoromethyl)-

HRID 1030784

Reaction equation

HRID 1030784 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15](=[N:20]O)[C:16]([F:19])([F:18])[F:17])=[CH:10][CH:9]=1.Cl[CH:23]=[CH:24][C:25]#[N:26]>O1CCCC1.C(Cl)Cl>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:24]([C:25]#[N:26])=[CH:23][NH:20][C:15]=2[C:16]([F:19])([F:18])[F:17])=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 53439748beta-ChloroacrylonitrileHCID 85405208(p-Chlorophenyl)-1,1,1-trifluoro-2-propanone oxime

Product 1

HCID 118217011H-Pyrrole-3-carbonitrile, 4-(4-chlorophenyl)-5-(trifluoromethyl)-

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium-t-butoxide (2.46 g, 0.022 mol) is added in portions to a solution of 3-(p-chlorophenyl)-1,1,1-trifluoro-2-propanone oxime, (E)-, or (Z)-(4.75 g, 0.02 mol) in tetrahydrofuran (20 mL) at such a rate that the temperature if maintained at 25°-30° C. (ice-water bath). The resulting solution is stirred for 15 minutes and then added dropwise to a solution of β-chloroacrylonitrile (1.75 g, 0.02 mol) in tetrahydrofuran (15 mL) at 15°-10° C. over 1/2 hour. The ice bath is removed and the reaction mixture is stirred for 1 hour, diluted with water, made acidic with a small amount of dilute HCl and extracted with ether. The combined ether extracts are washed with water and brine and dried (Na2SO4). Concentration in vacuo gives an oil which is dissolved in methylene chloride and filtered through a bed of flash column silica gel (30 mL size) and washed with an ethyl acetate/methylene chloride mixture (1:1). The filtrate is evaporated and the residual semi-solid is crystallized from methylene chloride/hexanes to give the title product as a yellow solid (2.10 g): mp 162.5°-164.0° C. IR (Nujol) 3200, 2250 cm-1, 1H NMR (DMSO-d6) δ7.42, 7.56 (AB, JAB =8.3 Hz, ArH), 8.03 (s, 1H, 2H); 19F NMR δ-51.2; 13C NMR δ94.2 (C-3), 115.0 (CN), 116.6 (q, 2JCF =38.3 Hz, C-5), 120.6 (q, 1JCF =268.7 Hz, CF3), 127.0 (q, 3JCF =3.5 Hz, C-4), 128.6 (C-2') 129.1 (C-1'), 129.7 (C-2), 130.8 (C-3'), 133.4 (C-4').

Workup

  1. customThe ice bath is removed
  2. stirringthe reaction mixture is stirred for 1 hour
  3. additiondiluted with water
  4. extractionextracted with ether
  5. washThe combined ether extracts are washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationConcentration in vacuo
  8. customgives an oil which
  9. filtrationfiltered through a bed of flash column silica gel (30 mL size)
  10. washwashed with an ethyl acetate/methylene chloride mixture (1:1)
  11. customThe filtrate is evaporated
  12. customthe residual semi-solid is crystallized from methylene chloride/hexanes

Sources & evidence

ORD record
ord-52a6139fe5294b749e0bbaf6550724e8
Source dataset
uspto-grants-1992_04
Patent number
US05106985

Linked notes

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