Benzene, 1-iodo-4-(trifluoromethyl)- → Tert-butyl({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methyl)carbamate

HRID 2093585Notes

Reaction equation

CC(C)([O-])C.[Na+].I[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.[C:18]([O:22][C:23](=[O:32])[NH:24][CH2:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:21])([CH3:20])[CH3:19]>C1(C)C=CC=CC=1>[C:18]([O:22][C:23](=[O:32])[NH:24][CH2:25][CH:26]1[CH2:27][CH2:28][N:29]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH2:30][CH2:31]1)([CH3:21])([CH3:19])[CH3:20]

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of sodium tert-butoxide, 1-iodo-4-(trifluoromethyl)benzene (686 μl) and tert-butyl(piperidin-4-ylmethyl)carbamate (1.00 g) in toluene (10 ml) was added 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (286 mg) and tris-dibenzylideneacetone palladium(0) (211 mg). The mixture was heated to 90° C. for 15 h. The mixture was cooled to room temperature, concentrated in vacuo, and diluted with dichloromethane. This solution was filtered through a short plug of silica gel and concentrated. The residue was purified via flash chromatography on a Biotage Horizon, 40M column, eluting with 10 column volumes of 33% ethyl acetate in hexanes to provide 1.36 g (81%) of the title compound. Mass spectrum (ESI) 303.0 (M+1).

Workup

temperatureThe mixture was cooled to room temperature
concentrationconcentrated in vacuo
additiondiluted with dichloromethane
filtrationThis solution was filtered through a short plug of silica gel
concentrationconcentrated
customThe residue was purified via flash chromatography on a Biotage Horizon, 40M column
washeluting with 10 column volumes of 33% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-da5922ce19fd44abbf9d1f07370a4bf1
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445480B2

Reaction notes

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