Trifluoroacetamide → 2,2,2-trifluoro-N-(4-(3-hydroxyphenyl)butyl)acetamide

HRID 517171Notes

Reaction equation

HRID 517171 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([NH2:5])=[O:4].O.[C:9]1(C)[CH:14]=[CH:13][C:12](S(O)(=O)=O)=[CH:11][CH:10]=1.C([O-])(O)=O.[Na+].[Cl-].[Na+].O.[CH2:28]1[CH2:32][O:31][CH2:30][CH2:29]1.O>>[F:1][C:2]([F:7])([F:6])[C:3]([NH:5][CH2:13][CH2:12][CH2:11][CH2:10][C:9]1[CH:32]=[CH:28][CH:29]=[C:30]([OH:31])[CH:14]=1)=[O:4]

Participants

5

Reactant 4

HCID 67717TrifluoroacetamideHCID 521998p-Toluenesulfonic acid monohydrateHCID 21881883Oxolane--water (1/1)HCID 129703874Sodium hydrogencarbonate brine

Product 1

HCID 866284752,2,2-trifluoro-N-(4-(3-hydroxyphenyl)butyl)acetamide

Procedure

A mixture of THP-phenol 136 (0.72 g, 2.08 mmol), p-toluenesulfonic acid monohydrate (0.366 g) in THF:H2O (3:1, 20 mL) was stirred at room temperature for 3.5 hr. The reaction mixture was treated with aqueous NaHCO3-brine solution, layers were separated and aqueous layer extracted with EtOAc. Combined organic layers were washed with brine and concentrated under reduced pressure. Purification by flash chromatography (10%-50% EtOAc-hexanes gradient) gave 2,2,2-trifluoro-N-(4-(3-hydroxyphenyl)butyl)acetamide as a colorless oil, which was taken into the next step. Yield (0.438 g, 96%).

Workup

  1. customwere separated
  2. extractionaqueous layer extracted with EtOAc
  3. washCombined organic layers were washed with brine
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (10%-50% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-38f3a3320adf4afca65b573a9cfd8404
Source dataset
uspto-grants-2015_08
Patent number
US09115056B2

Reaction notes

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