Cyclobutanone → 1-(4-Fluorophenyl)-2-(1-hydroxycyclobutan-1-yl) ethan-1-one
Reaction equation
[C:1]1(=[O:5])[CH2:4][CH2:3][CH2:2]1.[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([O:15][Si](C)(C)C)=[CH2:14])=[CH:9][CH:8]=1>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH2:14][C:1]2([OH:5])[CH2:4][CH2:3][CH2:2]2)=[CH:9][CH:8]=1Participants
Procedure
Under nitrogen, 11.0 g (100 mmol) of titanium(IV) chloride in 140 mL of methylene chloride at 0° C. was slowly treated with a solution of 8.2 mL (110 mmol) of cyclobutanone in 30 mL of methylene chloride prior to the dropwise addition of a solution of 21.1 g (100 mmol) of 1-fluoro-4-[1[(trimethylsilyl)oxy]ethenyl]benzene (obtained from Step 2) in 15 mL of methylene chloride. The reaction was stirred for 15 minutes and then poured into 200 mL of ice/water; the phases were separated. The aqueous phase was extracted twice with 30 mL of methylene chloride and combined with the original methylene chloride phase. The combined extracts were washed 3 times with 120 mL of saturated sodium carbonate/water (1:1) and once with brine, dried (MgSO4), and concentrated in vacuo to give 20.4 g (98%) of crude 1-(4-fluorophenyl)-2-(1-hydroxycyclobutan-1-yl) ethan-1-one as an oil: NMR (CDCl3) δ 1.53-1.70 (m, 1H), 1.80 -1.94 (m, 1H), 1.99-2.10 (m, 2H), 2.17-2.31 (m, 2H), 3.31 (s, 2H), 7.10-7.19 (m, 2H), 7.95-8.03 (m, 2H).
Workup
- customthe phases were separated
- extractionThe aqueous phase was extracted twice with 30 mL of methylene chloride
- washThe combined extracts were washed 3 times with 120 mL of saturated sodium carbonate/water (1:1)
- dry with materialonce with brine, dried (MgSO4)
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-14b8f30984094f138cff15a8c3a5ce32
- Source dataset
- uspto-grants-1995_02
- Patent number
- US05393790
Reaction notes
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