Benzene, 1-fluoro-4-(trifluoromethyl)- → 1-(4-(Trifluoromethyl)phenyl)cyclopentanecarbonitrile

HRID 719671Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[CH:12]1([C:17]#[N:18])[CH2:16][CH2:15][CH2:14][CH2:13]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1(C)C=CC=CC=1>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([C:12]2([C:17]#[N:18])[CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of 4-fluorobenzotrifluoride (5.0 g, 30.47 mmol) in toluene (40 mL) was added cyclopentanecarbonitrile (10.5 mL, 100.55 mmol) followed by a solution of 0.5 M KHMDS in toluene (92 mL, 45.71 mmol). The reaction mixture was heated to 70° C. and stirred for 14 hours. After cooling to RT, the reaction mixture was quenched with 1 M HCl until pH<7. The layers were separated and the organic layer was washed with saturated NaHCO3, water, brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification via silica gel chromatography (6:1 hexanes:EtOAc) afforded 7.53 g of a mixture of compound A and residual cyclopentanecarbonitrile. Because these two compounds were not easily separable by chromatography, this mixture was carried directly to the next step.

Workup

temperatureAfter cooling to RT
customthe reaction mixture was quenched with 1 M HCl until pH<7
customThe layers were separated
washthe organic layer was washed with saturated NaHCO3, water, brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification via silica gel chromatography (6:1 hexanes:EtOAc)

Sources & evidence

ORD record: ord-abb08ea1e0a547d09b41411d6d1b90bb
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07132443B2

Reaction notes

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