Potassium Phosphate, Tribasic → 1-(2-{4-[2-(2,6-Difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine

HRID 1513919Notes

Reaction equation

HRID 1513919 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]=[C:40]([F:44])[C:39]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[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

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343362,6-Difluorophenylboronic acidHCID 57552542Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-yl-ethoxy)-benzyl]-naphthalen-2-yl ester

Product 1

HCID 575525411-(2-{4-[2-(2,6-Difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidineYield 58%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-yl ester (1.50 g, 2.86 mmol) in 50 mL of acetonitrile and add 2,6-difluorophenyl boronic acid (0.90 g, 5.73 mmol), tetrakis(triphenylphosphine)palladium(0) (0.66 g, 0.57 mmol). Next add potassium phosphate (3.64 g, 17.16 mmol) and heat to 80° C. for one hour. Add Celite and filter. Concentrate the solvent under vacuum to a dark oil, dissolve in methanol and purify on an SCX cartridge, eluting with 2N ammonia/methanol. Purify further on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient. Evaporate the solvent to yield 800 mg (58%) of the title compound.

Workup

  1. filtrationAdd Celite and filter
  2. concentrationConcentrate the solvent under vacuum to a dark oil
  3. dissolutiondissolve in methanol
  4. custompurify on an SCX cartridge
  5. washeluting with 2N ammonia/methanol
  6. customPurify further on a silica gel column
  7. washeluting with a 0-10% methanol/methylene chloride gradient
  8. customEvaporate the solvent

Sources & evidence

ORD record
ord-93120cdd28e24918927f9a40aebab702
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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