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

HRID 1513851Notes

Reaction equation

HRID 1513851 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O: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+]>CN(C=O)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[O: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 116133766-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl trifluoromethanesulfonate

Product 1

HCID 113407861-(2-{4-[2-(2,6-Difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidineYield 32.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester (1.0 gm., 1.9 mmoles) in 20 ml DMF. To this solution add 2,6-difluorophenylboronic acid (0.6 gm., 3.8 mmoles), potassium phosphate (2.42 gm., 11.4 mmoles) and tetrakis(triphenylphosphine)palladium (0) (0.44 gm., 0.38 mmoles) and heat to 100° C. for 18 hours. Cool and filter the mixture and purify on an SCX column, eluting the impurities with methanol, then eluting the product with 2N ammonia/methanol. Purify further on a silica gel column eluting with a gradient of 50-100% methylene chloride/hexane containing 1% isopropyl amine to give 300 mg (32%) of the title compound.

Workup

  1. temperatureCool
  2. filtrationfilter the mixture
  3. custompurify on an SCX column
  4. washeluting the impurities with methanol
  5. washeluting the product with 2N ammonia/methanol
  6. customPurify further on a silica gel column
  7. washeluting with a gradient of 50-100% methylene chloride/hexane containing 1% isopropyl amine

Sources & evidence

ORD record
ord-f3f0002489a44155a0c0a698ef62e3d5
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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