Tetrahydrofuran → 1-(2'-Fluoro-4-(hydroxymethyl)-5'-(methyloxy)-1,1'-biphenyl-2-yl)-2,2-dimethyl-1-propanone
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[C:11]([C:18]([O:20]C)=O)=[CH:12][C:13]([CH2:16][OH:17])=[CH:14][CH:15]=1.C1COCC1.[C:27]([Li])([CH3:30])([CH3:29])[CH3:28].[Cl-].[NH4+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][OH:17])=[CH:12][C:11]=1[C:18](=[O:20])[C:27]([CH3:30])([CH3:29])[CH3:28]Participants
Reactant 4
Product 1
Procedure
To a stirred solution of methyl 2′-fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-carboxylate T9.5 (2.00 g, 7 mmol) in THF (138 mL, 7 mmol) at −78° C. was added t-butyllithium (1.7 M in pentane, 9 mL, 14 mmol). Stirring was continued for 3 hours. A saturated solution of ammonium chloride was added to quench the reaction, and the resulting mixture was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give the residue. The residue was purified by silica gel flash chromatography (0-20% EtOAc/hexane) to afford 1-(2′-Fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-yl)-2,2-dimethyl-1-propanone T9.6 as a clear oil (2.00 g, 92% yield). MS ESI (pos.) m/e: 334.1 (M+H2O)+, 317.2 (M+H)+.
Workup
- customto quench
- customthe reaction
- extractionthe resulting mixture was extracted with EtOAc
- dry with materialThe combined organic layers were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give the residue
- customThe residue was purified by silica gel flash chromatography (0-20% EtOAc/hexane)
Sources & evidence
- ORD record
- ord-a7186887426f44ad9e3b0dc04ce13124
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08450522B2
Reaction notes
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