Cesium fluoride → 1-(2-{4-[6-Methoxy-2-(2,3,4,5-tetrafluoro-phenyl)-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine

HRID 1513918Notes

Reaction equation

HRID 1513918 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.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.[F-].[Cs+].Br[C:58]1[CH:63]=[C:62]([F:64])[C:61]([F:65])=[C:60]([F:66])[C:59]=1[F:67]>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Pd].C(#N)C>[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]([C:58]1[CH:63]=[C:62]([F:64])[C:61]([F:65])=[C:60]([F:66])[C:59]=1[F:67])[CH:7]=[CH:6]2

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 661771-Bromo-2,3,4,5-tetrafluorobenzeneHCID 2733548Bis(pinacolato)diboraneHCID 57552542Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-yl-ethoxy)-benzyl]-naphthalen-2-yl ester

Product 1

HCID 113868881-(2-{4-[6-Methoxy-2-(2,3,4,5-tetrafluoro-phenyl)-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidineYield 73.3%

Reagents, catalysts & solvents 2

HCID 2734559Bis(tricyclohexylphosphine) palladium(0)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-yl ester (259 mg, 0.49 mmol), bis(pinacolato)diboron (151 mg, 0.59 mmol), bis(tricyclohexylphosphine)palladium (0) (75 mg, 0.11 mmol) and cesium fluoride (764 mg, 5.03 mmol) in 20 mL degassed acetonitrile and heat at 100° C. under nitrogen in a sealed vial. The reaction is complete in 10 minutes. Cool and add 1-bromo-2,3,4,5-tetrafluorobenzene (224 mg, 0.99 mmol) along with 10 mL acetonitrile, seal the vial, purge with nitrogen and heat at 80° C. for 2 hours. Cool, filter and purify on an SCX column eluting with 2N ammonia/methanol. Evaporate the solvent and purify the resulting oil on a silica column eluting with 3% methanol/methylene chloride to give 188 mg of the title compound (73%).

Workup

  1. customdegassed acetonitrile
  2. temperatureCool
  3. customseal the vial,
  4. custompurge with nitrogen
  5. temperatureheat at 80° C. for 2 hours
  6. temperatureCool
  7. filtrationfilter
  8. custompurify on an SCX column
  9. washeluting with 2N ammonia/methanol
  10. customEvaporate the solvent
  11. custompurify the resulting oil on a silica column
  12. washeluting with 3% methanol/methylene chloride

Sources & evidence

ORD record
ord-3b3688b38e9942bfaed5d7c8b2ee704c
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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