Trifluoroacetic acid → 4-(Adamantan-1-ylmethoxy)-3-cyclobutylbenzonitrile

HRID 1427887Notes

Reaction equation

[C:1]12([CH2:11][O:12][C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3[C:21]3(O)[CH2:24][CH2:23][CH2:22]3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl.[OH-].[Na+]>[C:1]12([CH2:11][O:12][C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3[CH:21]3[CH2:24][CH2:23][CH2:22]3)[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2

Participants

Conditions

Temperature: 0 °C

Procedure

To a cooled (0° C.) stirred solution of 4-(adamantan-1-ylmethoxy)-3-(1-hydroxycyclobutyl)-benzonitrile (1.00 g, 2.96 mmol) in methylene chloride (30 mL) was added triethylsilane (2.4 mL, 14.80 mmol) followed by trifluoroacetic acid (2.3 mL, 29.60 mmol). The reaction mixture was stirred at 0° C. for 1.5 h and diluted with 1M aqueous sodium hydroxide solution (30 mL). The mixture was extracted with methylene chloride (3×50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 5% to 10% gradient of ethyl acetate in hexanes to afford 4-(adamantan-1-ylmethoxy)-3-cyclobutylbenzonitrile as colorless solid in quantitative yield (0.95 g): MS (ES+) m/z 322.2 (M+1);

Workup

extractionThe mixture was extracted with methylene chloride (3×50 mL)
washThe combined organic layers were washed with brine (50 mL)
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography
washeluting with a 5% to 10% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record: ord-b17c9a45da384c52920f09d5c424c598
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933236B2

Reaction notes

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