Hydrochloric Acid → 4-(2,5-Dioxo-2,5-dihydro-1h-pyrrol-1-yl)-2-(trifluoromethyl)benzonitrile

HRID 966938Notes

Reaction equation

HRID 966938 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]=[CH:13][C:14]([OH:16])=O)=[O:11])=[CH:5][C:4]=1[C:17]([F:20])([F:19])[F:18])#[N:2].C1(C)C=CC=CC=1.C[Si](C)(C)N[Si](C)(C)C.Cl>CCOC(C)=O.[Br-].[Zn+2].[Br-].CCCCCCC>[O:16]=[C:14]1[CH:13]=[CH:12][C:10](=[O:11])[N:9]1[C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:17]([F:20])([F:19])[F:18])[CH:5]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1140Toluene2×HCID 13838HexamethyldisilazaneHCID 685405383-(4-Cyano-3-trifluoromethylphenylcarbamoyl)acrylic acid

Product 1

HCID 218749284-(2,5-Dioxo-2,5-dihydro-1h-pyrrol-1-yl)-2-(trifluoromethyl)benzonitrileYield 86.3%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
60 °C

Procedure

Compound 516A (17.42 mmoles, 5.000 g) was added to the reaction flask followed by the addition of zinc bromide (17.58 mmoles, 3.960 g) and then toluene (50.00 mL, 43.25 g) was added to the mixture. The resulting suspension was stirred for 20 min. Hexamethyldisilazane (26.35 mmoles, 5.560 mL, 4.253 g) was added to this suspension which was then heated to 60° C. for 4.5 h. The reaction mixture was diluted with EtOAc (25 mL) and then poured into a 1N HCl solution (30 mL) at 25° C. The organic phase was collected and the aqueous phase was extracted with EtOAc (15 mL). The organic phase was isolated, combined with the earlier organic phase and washed consecutively with saturated NaHCO3 (15 mL), a mixture of 1:1 water:brine solution (15 mL) and brine (15 mL). The resulting solution was dried over MgSO4, filtered and concentrated in vacuo to a 50 mL suspension. Heptane (125 mL) was added dropwise to this suspension with agitation. The resulting thicker suspension was filtered and washed with a mixture of 2:1 heptane:toluene (15 mL) and then heptane (15 mL) to give 4 g (85% yield) of compound 516B. HPLC: 100% at 2.11 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).

Workup

  1. customThe organic phase was collected
  2. extractionthe aqueous phase was extracted with EtOAc (15 mL)
  3. customThe organic phase was isolated
  4. washwashed consecutively with saturated NaHCO3 (15 mL)
  5. additiona mixture of 1:1 water
  6. dry with materialThe resulting solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a 50 mL suspension
  9. additionHeptane (125 mL) was added dropwise to this suspension with agitation
  10. filtrationThe resulting thicker suspension was filtered
  11. washwashed with a mixture of 2:1 heptane

Sources & evidence

ORD record
ord-06c84d477f1f40f08660592b11b86afd
Source dataset
uspto-grants-2005_10
Patent number
US06953679B2

Reaction notes

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