Ethanol → 4,4,4-Trifluoro-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-butyronitrile

HRID 40913Notes

Reaction equation

HRID 40913 reaction equation
[F:1][C:2]([F:30])([F:29])[CH:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][N:18](COCC[Si](C)(C)C)[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][C:5]#[N:6].C1COCC1.C([O-])(O)=O.[Na+].C(O)C.[OH-].[NH4+]>Cl.O.C(OCC)(=O)C>[F:30][C:2]([F:1])([F:29])[CH:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][NH:18][C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][C:5]#[N:6]

Participants

9

Reactant 5

HCID 702EthanolHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 516892Sodium BicarbonateHCID 574776494,4,4-Trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

Product 1

HCID 177542644,4,4-Trifluoro-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-butyronitrileYield 138%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (3.1 g, 0.0071 mol) from Step 1 in THF (35 mL, 0.43 mol) and 3.0 M HCl in water (35 mL) was heated to reflux overnight. The solvent was removed by rotary evaporation to give a greenish orange oil/glass. The oil was stirred with ethyl acetate and sat. NaHCO3 (50 mL). The aqueous phase was extracted with ethyl acetate. The organic layers were washed with brine and reduced by rotary evaporation to give an oil/glass residue. The residue was stirred in ethanol (20 mL, 0.3 mol) and 8.0 M ammonium hydroxide in water (10 mL) over a weekend. The solvent was removed by rotary evaporation to give a pale orange foam/solid. The crude was chromatographed with 0-7% MeOH/DCM, 0-0.7% NH4OH to give 3 g of a pale orange paste/solid. The solid was recrystallized from EtOH to give 1.6 g of an off-white crystals (74% yield).

Workup

  1. temperatureto reflux overnight
  2. customThe solvent was removed by rotary evaporation
  3. customto give a greenish orange oil/glass
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. washThe organic layers were washed with brine
  6. customreduced by rotary evaporation
  7. customto give an oil/glass residue
  8. customThe solvent was removed by rotary evaporation
  9. customto give a pale orange foam/solid
  10. customThe crude was chromatographed with 0-7% MeOH/DCM, 0-0.7% NH4OH

Sources & evidence

ORD record
ord-1324a86f7fdc45e1add79b24b4f6f47e
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

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