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 T4.4 (2.00 g, 7 mmol) in THF (138 mL, 7 mmol) at −78° C. was added t-butyllithium (1.7M in pentane, 9 mL, 14 mmol). The resulting mixture was then stirred 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. 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 T4.5 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
- customThe residue was purified by silica gel flash chromatography (0-20% EtOAc/hexane)
Sources & evidence
- ORD record
- ord-1c8f58090c8e49598175f744f26fab3e
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08748462B2
Reaction notes
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