Water → HCID 54228616, compound

HRID 1262424Notes

Reaction equation

HRID 1262424 reaction equation
[C:1]1([C:7]2([C:19]#[N:20])[CH2:12][CH2:11][N:10]([C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[N+:34]([O-])([O-:36])=[O:35].[K+].O>C(#N)C>[N+:34]([C:4]1[CH:3]=[CH:2][C:1]([C:7]2([C:19]#[N:20])[CH2:8][CH2:9][N:10]([C:13](=[O:18])[C:14]([F:16])([F:17])[F:15])[CH2:11][CH2:12]2)=[CH:6][CH:5]=1)([O-:36])=[O:35]

Participants

6

Reactant 4

HCID 962WaterHCID 9845Trifluoroacetic anhydrideHCID 24434Potassium NitrateHCID 53678614HCID 53678614, compound

Product 1

HCID 54228616HCID 54228616, compoundYield 31.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

4-Phenyl-1-(2,2,2-trifluoro-acetyl)-piperidine-4-carbonitrile was dissolved in Acetonitrile (12.0 mL), Trifluoroacetic anhydride (4.00 mL, 28.3 mmol) was added and the mixture was cooled in an ice bath. Potassium nitrate (1.58 g, 15.6 mmol) was then added and the reaction was stirred at 0° C. for 2 h, then water (100 mL) was added at 0° C. The mixture was extracted with EtOAc (2×50 mL), the organics were washed with 1:1 brine:satd. NaHCO3 (2×50 mL), dried over sodium sulfate and then filtered through 8 mL silica gel, washing with 100 mL EtOAc. The filtrate was conc. in vacuo. 1H-NMR indicated a mixture of nitration products and starting material. Resubjection to the nitration conditions (12 mL MeCN, 4 mL TFAA, 1.59 g KNO3, rt, overnight). Work up as before, conc. in vacuo to afford an oil, 1H-NMR showing -2.6:1 ratio of nitration products. The crude oil was dried in vacuo and then dissolved in DCM, loaded onto a 25 g ISCO cartridge and purified (120 g column, 0%, then 5-30% EtOAc:Hex) to afford partial separation of the nitro products, the major eluting first. Clean fractions were conc. in vacuo to afford 4-(4-Nitro-phenyl)-1-(2,2,2-trifluoro-acetyl)-piperidine-4-carbonitrile (1.29 g; Yield=31.4%) as a white solid. 1H-NMR (DMSO-d6): 8.31 (d, 2H, J=8.8 Hz), 7.91 (d, 2H, J=8.8 Hz), 4.52 (m, 1H), 4.07 (m, 1H), 3.55 (m, 1H), 3.17 (m, 1H), 2.27 (m, 4H).

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. extractionThe mixture was extracted with EtOAc (2×50 mL)
  3. washthe organics were washed with 1:1 brine
  4. dry with materialNaHCO3 (2×50 mL), dried over sodium sulfate
  5. filtrationfiltered through 8 mL silica gel
  6. washwashing with 100 mL EtOAc
  7. additiona mixture of nitration products
  8. customto the nitration conditions (12 mL MeCN, 4 mL TFAA, 1.59 g KNO3, rt, overnight)
  9. customto afford an oil
  10. customThe crude oil was dried in vacuo
  11. dissolutiondissolved in DCM
  12. custompurified (120 g column, 0%
  13. custom5-30% EtOAc:Hex) to afford partial
  14. customseparation of the nitro products
  15. washthe major eluting first

Sources & evidence

ORD record
ord-8289f64c2f094bd3a76d82d52378c324
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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