Hydrochloric Acid → 2,2,2-Trifluoro-N-phenylacetamide

HRID 2081692Notes

Reaction equation

HRID 2081692 reaction equation
Br[C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[NH:4][C:5](=[O:10])[C:6]([F:9])([F:8])[F:7].C[Li].C([Li])(C)(C)C.ClC1CC2C(=CC=CC=2)C1=O.[OH-].[K+].Cl>O1CCCC1.C(OCC)C.CCCCC.CO>[F:7][C:6]([F:8])([F:9])[C:5]([NH:4][C:3]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:2]=1)=[O:10]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 526932-Chloro-2,3-dihydro-1H-inden-1-oneHCID 4263215N-(2-Bromophenyl)-2,2,2-trifluoroacetamideHCID 178418306HCID 178418306, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 678812,2,2-Trifluoro-N-phenylacetamideYield 21.8%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of o-bromotrifluoroacetanilide (325 mg, 1.2 mM) in tetrahydrofuran (THF)(20 cm3) was cooled to -78° C. and to this was added methyl lithium (1 molar equivalent of a 1.4 M solution in diethyl ether). This addition was followed 10 minutes later by the introduction of tert-butyllithium (2 molar equivalent of a 1.7 M solution in pentane). The reaction mixture was stirred for 1 hour at -78° C., and then a solution of the chloroindanone (272 mg. 1.2 mM) in THF (3 cm3) added dropwise via a cannula. The solution was allowed to warm slowly to room temperature, and stirred for one hour, then a 10% solution potassium hydroxide in methanol (3 cm3) was introduced. After stirring for 30 minutes, the reaction mixture was poured into 2 M HCl, and extracted with dichloromethane (3 ×10 cm3). The combined organic extracts were dried (Na2SO4 ) and evaporated in vacuo to afford a solid residue which was chromatographed on silica, eluting with 10% ethyl acetate/petroleum ether (60°-80° C.) to yield trifluoroacetanilide (RF 0.4)(50 mg), and the 2-chloro-1-hydroxy-5-methoxy-4,6-dimethyl-1-(2'-trifluoroacetamidophenyl)indane (RF 0.3) (220 mg, 44%). The latter compound is a colourless solid. M.p. 182° C. 1H NMR (CDCl3)δ: 10.7 (1H, br), 8.25 (1H, dd), 7.36 (1H, ddd), 7.06 (1H, s), 6.98 (1H, ddd), 6.39 (1H, dd), 4.76 (1H, dd, J=4.8, 2.7Hz), 3.78 (3H, s), 3.63 (1H, s, exchanges with D2O), 3.11 (2H, 2 ×2nd order multiplets), 2.33 (3H, s), 2.23 (3H, s).

Workup

  1. additionThis addition
  2. temperatureto warm slowly to room temperature
  3. stirringstirred for one hour
  4. stirringAfter stirring for 30 minutes
  5. extractionextracted with dichloromethane (3 ×10 cm3)
  6. dry with materialThe combined organic extracts were dried (Na2SO4 )
  7. customevaporated in vacuo
  8. customto afford a solid residue which
  9. customwas chromatographed on silica
  10. washeluting with 10% ethyl acetate/petroleum ether (60°-80° C.)

Sources & evidence

ORD record
ord-1e9894d32c674c8e8d6f6189511c54a3
Source dataset
uspto-grants-1993_02
Patent number
US05185360

Reaction notes

Loading…