Trifluoroacetic acid → HCID 67283106, compound

HRID 1890390Notes

Reaction equation

HRID 1890390 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([C:17]([F:20])([F:19])[F:18])[CH:10]=2)[CH2:4][CH2:3]1.[H-].[Na+].C([O:27][C:28](=[O:30])[CH3:29])(C)(C)C.FC(F)(F)C(O)=O>O1CCCC1.C(OCC)(=O)C.ClCCl.O>[C:13]([C:12]1[CH:15]=[CH:16][C:9]([NH:8][CH:5]2[CH2:6][CH2:7][CH:2]([O:1][CH2:29][C:28]([OH:30])=[O:27])[CH2:3][CH2:4]2)=[CH:10][C:11]=1[C:17]([F:18])([F:19])[F:20])#[N:14]

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10908tert-Butyl acetateHCID 24758Sodium hydrideHCID 56784866HCID 56784866, compound

Product 1

HCID 67283106HCID 67283106, compoundYield 39%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

4-(4-Hydroxy-cyclohexylamino)-2-trifluoromethyl-benzonitrile (4.30 mmol) is dissolved in dry tetrahydrofuran (10 mL) and sodium hydride (60% suspension in oil, 13.0 mmol) is added. The resulting mixture is stirred for 15 minutes and is cooled down to 5° C. prior to the addition of acetic acid tert-butyl ester (4.30 mmol). After 1.5 hours reaction time, water (7 mL) is slowly added under vigorous stirring and the mixture is then diluted with ethyl acetate (25 mL). The organic phase is collected and is concentrated under reduced pressure. The residue obtained is then treated with a 1 to 1 mixture of dichloromethane and trifluoroacetic acid (10 mL). After 2 hours, the reaction mixture is concentrated under reduced pressure. The residue obtained is taken up in dichloromethane (20 mL) and the organic phase is extracted with aqueous 3N sodium hydroxide solution (3×7 mL) and washed with water (2×5 mL). The pH of all combined aqueous phases is then brought to 5-6 by the addition of aqueous 5N hydrochloric acid. The acidic aqueous phase is extracted with dichloromethane (4×15 mL) and the combined organic layers are dried over magnesium sulphate, filtered and concentrated under reduced pressure to afford the desired acid (39% yield).

Workup

  1. additionis slowly added
  2. stirringunder vigorous stirring
  3. customThe organic phase is collected
  4. concentrationis concentrated under reduced pressure
  5. customThe residue obtained
  6. waitAfter 2 hours
  7. concentrationthe reaction mixture is concentrated under reduced pressure
  8. customThe residue obtained
  9. extractionthe organic phase is extracted with aqueous 3N sodium hydroxide solution (3×7 mL)
  10. washwashed with water (2×5 mL)
  11. additionThe pH of all combined aqueous phases is then brought to 5-6 by the addition of aqueous 5N hydrochloric acid
  12. extractionThe acidic aqueous phase is extracted with dichloromethane (4×15 mL)
  13. dry with materialthe combined organic layers are dried over magnesium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6dc8f6c88ff2465da8b124acd84d0aad
Source dataset
uspto-grants-2013_08
Patent number
US08507474B2

Reaction notes

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