Ethylene Glycol → 1-(3-Fluorophenyl)cyclobutane-1-carboxylic acid
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2([C:12]#N)[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[OH-:14].[K+].C(O)C[OH:18]>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2([C:12]([OH:18])=[O:14])[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 150 °C
Procedure
A mixture of 1-(3-fluorophenyl)cyclobutanecarbonitrile (7.41 g, 42.3 mmol) and powdered potassium hydroxide (7.0 g, 125 mmol) in ethylene glycol (100 mL) is heated at 150° C. for 7 hours. The cooled reaction mixture is diluted with ice water (140 mL) and extracted with ether (3×100 mL). The combined organics are washed with water (2×35 mL). The combined aqueous washings are cooled to 0° C. and brought to pH 3 with 6 N aqueous hydrochloric acid (30 mL). Nitrogen is bubbled through the solution to give a solid precipitate. The solid is isolated by filtration, washed with water and dried in a vacuum oven at 60° C. for 48 hours to afford 7.04 g of 1-(3-fluorophenyl)cylobutanecarboxylic acid. 1H NMR (CDCl3) δ7.27 (m, 2 H), 7.00 (m, 4 H), 2.84 (m, 2 H), 2.48 (m, 2 H), 2.10 (m, 1 H), 1.93 (m, 1 H).
Workup
- customThe cooled reaction mixture
- extractionextracted with ether (3×100 mL)
- washThe combined organics are washed with water (2×35 mL)
- temperatureThe combined aqueous washings are cooled to 0° C.
- customNitrogen is bubbled through the solution
- customto give a solid precipitate
- customThe solid is isolated by filtration
- washwashed with water
- customdried in a vacuum oven at 60° C. for 48 hours
Sources & evidence
- ORD record
- ord-4121e958146d4613b46347ffd5755be3
- Source dataset
- uspto-grants-1996_06
- Patent number
- US05525742
Reaction notes
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