Hydrochloric Acid → HCID 13440335, compound

HRID 911270Notes

Reaction equation

HRID 911270 reaction equation
[F:1][C:2]([F:7])([F:6])[CH:3]([OH:5])[CH3:4].[H-].[Na+].F[C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1.Cl>CN(P(N(C)C)(N(C)C)=O)C>[F:1][C:2]([F:7])([F:6])[CH:3]([CH3:4])[O:5][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 97741,1,1-Trifluoro-2-propanolHCID 145174-FluorobenzonitrileHCID 24758Sodium hydride

Product 1

HCID 13440335HCID 13440335, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
90 °C

Procedure

Add 1,1,1-trifluoro-2-propanol (3.8 g, 66 mmol) slowly to a slurry of sodium hydride (730 mg, 60% in mineral oil, washed with hexane) in HMPA (5 mL) under nitrogen. Stir the slurry for 15 min and add 4-fluorobenzonitrile (2 g, 16.5 mmol). Heat the slurry in a sealed flask to 90° C. for 16 h. Cool the mixture to ambient temperature and pour the mixture into a flask containing 5% aqueous HCl (20 mL). Extract the mixture with diethyl ether (3×50 mL), and wash with 5% aqueous HCl (25 mL). Dry the organic layer over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to obtain the desired intermediate (2.5 g, 70%). GC-MS m/z: 215 (M+).

Workup

  1. temperatureCool the mixture to ambient temperature
  2. additionpour the mixture into a flask
  3. extractionExtract the mixture with diethyl ether (3×50 mL)
  4. washwash with 5% aqueous HCl (25 mL)
  5. dry with materialDry the organic layer over Na2SO4
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-ae69009ce4c347959be510d8fad56935
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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