Hydrochloric Acid → 1-(1-(4-(Trifluoromethyl)phenyl)cyclobutyl)ethanone

HRID 2110314Notes

Reaction equation

[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2(C#N)[CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C[Mg+].[Br-].CC[O:22][CH2:23][CH3:24].O.Cl>C1(C)C=CC=CC=1>[F:1][C:2]([F:15])([F:16])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2([C:23](=[O:22])[CH3:24])[CH2:12][CH2:11][CH2:10]2)=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 95 °C

Procedure

The starting nitrile, 1-(4-Trifluoromethyl-phenyl)-cyclobutanecarbonitrile, has been described (Parke Davis & Co., U.S. Pat. No. 3,536,656; 1970 and Chemical Abstracts 1970, 73, 109539). To the carbonitrile (2 g) in 5 mL of toluene in a pressure tube was added 10 mL of 3M MeMgBr ether solution (3 equiv.). The tube was sealed and the reaction mixture was heated at 95° C. for 24 hr, cooled to room temperature, poured into 50 mL of water, acidified with 25 mL of 5 M HCl, and this solution was heated at 70° C. for 2 h, cooled, and extracted with ether. The extracts were dried, filtered, concentrated, and purified on silica gel to give pure 1-[1-(4-trifluoromethyl-phenyl)-cyclobutyl]-ethanone (1.9 g, 88%). Data for this ketone: MS 242 (M); 1H NMR (300 MHz, CDCl3) δ 7.6 (d, 8.0 Hz, 2H), 7.4 (d, 8.0 Hz, 2H), 2.75-2.85 (m, 2H), 2.35-2.5 (m, 2H), 1.8-2.0 (3H s and 2H m overlapping); 13C NMR (75 MHz, CDCl3): δ 207.7, 147.5, 129.5, 126.9, 126.1, 125.9 (CF3), 59.5, 30.9, 24.6, 16.1.

Workup

customThe tube was sealed
temperaturecooled to room temperature
temperaturethis solution was heated at 70° C. for 2 h
temperaturecooled
extractionextracted with ether
customThe extracts were dried
filtrationfiltered
concentrationconcentrated
custompurified on silica gel

Sources & evidence

ORD record: ord-0c89a5389bc64ed7a87f3ef0bf22ff5a
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07517892B2

Reaction notes

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