Cesium fluoride → 1-(2-{4-[2-(2-Fluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine

HRID 1513915Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.[F:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1B(O)O.[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]=1[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-yl ester (1.0 g, 1.9 mmol), 2-fluorophenyl boronic acid (532 mg, 3.8 mmol), trans[dichlorobis(triphenylphosphine)]palladium II (266 mg, 0.38 mmol) and cesium fluoride (2.6 g, 17.1 mmol) in 150 mL degassed acetonitrile and heat at 85° C. for 2 hours. Cool the reaction, filter and purify on an SCX column, eluting with 2N ammonia/methanol. Concentrate and purify on a silica column eluting with 1 0-10% gradient of methanol/methylene chloride to give 560 mg (63%) of the title compound: mass spectrum (ion spray) m/z=470 (M+H).

Workup

customdegassed acetonitrile
temperatureCool
customthe reaction
filtrationfilter
custompurify on an SCX column
washeluting with 2N ammonia/methanol
concentrationConcentrate
custompurify on a silica column
washeluting with 1 0-10% gradient of methanol/methylene chloride

Sources & evidence

ORD record: ord-3c1565a250524ee9b2ce85d1e7b2f098
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217032B2

Reaction notes

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