Phenol → 2,2,2-Trifluoro-1-[5-fluoro-2-(2-propen-1-yloxy)phenyl]ethanone
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2([C:13]([F:16])([F:15])[F:14])CC[O:10]2)[CH:3]=1.F[C:18]1[CH:23]=CC(O)=C(C(O)C(F)(F)F)[CH:19]=1.C1(O)C=CC=CC=1.C(Br)C=C.C(=O)([O-])[O-].[K+].[K+]>>[F:16][C:13]([F:14])([F:15])[C:9]([C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[O:8][CH2:23][CH:18]=[CH2:19])=[O:10]Participants
6
Procedure
Synthesis of the requisite 4-fluoro-2-[2-(trifluoromethyl)oxetan-2-yl]phenol may be carried out from 4-fluoro-2-(2,2,2-trifluoro-1-hydroxyethyl)phenol (see J. Zhang et al., Synth. Commun. 2011, 41, 3045-3052). Selective alkylation of the phenol, using allyl bromide and a base such as potassium carbonate, followed by a Swern oxidation of the benzylic alcohol, provides 2,2,2-trifluoro-1-[5-fluoro-2-(prop-2-en-1-yloxy)phenyl]ethanone. This material was reacted with trimethylsulfoxonium iodide and potassium tert-butoxide to afford 2-[5-fluoro-2-(prop-2-en-1-yloxy)phenyl]-2-(trifluoromethyl)oxetane; the allyl group was removed using tetrakis(triphenylphosphine)palladium(0) and morpholine.
Sources & evidence
- ORD record
- ord-58c7be5b3b08488ea384ea96ffed4e92
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09067934B2
Reaction notes
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