Potassium Phosphate, Tribasic → [4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluorophenyl)-6-methoxy-naphthalen-1-yl]-methanone

HRID 1513903Notes

Reaction equation

HRID 1513903 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:38]=[CH:37][C:14]([C:15]([C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=4)[CH:20]=[CH:19][C:18]=3OS(C(F)(F)F)(=O)=O)=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:41]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.CN(C=O)C>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:38]=[CH:37][C:14]([C:15]([C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=4)[CH:20]=[CH:19][C:18]=3[C:41]3[C:40]([F:39])=[CH:45][CH:44]=[CH:43][C:42]=3[F:46])=[O:16])=[CH:13][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343362,6-Difluorophenylboronic acidHCID 57552509Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester

Product 1

HCID 57552543[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluorophenyl)-6-methoxy-naphthalen-1-yl]-methanone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Charge a flask with trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester (3.9 g, 7.06 mmol), 2,6-difluorophenyl boronic acid (2.23 g, 14.12 mmol), potassium phosphate (9.0 g, 42.20 mmol) and tetrakis(triphenylphosphine)palladium (0) (1.63 g, 1.40 mmol) followed by 125 mL dry DMF. Heat the mixture under nitrogen at 100° C. for 90 minutes. Cool, filter, evaporate the solvent and purify on an SCX cartridge, eluting with 2N ammonia/methanol. Purify further on a silica gel column eluting with 0-10% methanol/methylene chloride. The yield is 2.5 g (70%): 1H-NMR (CDCl3, 400 MHz) δ 7.90 (d, J=8.4 Hz, 1H); 7.66-7.61 (m, 3H); 7.39 (d, J=8.4 Hz, 1H); 7.23-7.22 (m, 1H); 7.18-7.08 (m, 2H); 6.79-6.74 (m, 4H); 4.08-4.05 (t, 2H); 3.95 (s, 3H); 2.96-2.89 (t, 2H); 2.78-2.75 (m, 4H); 1.66-1.59 (m, 8H).

Workup

  1. temperatureCool
  2. filtrationfilter
  3. customevaporate the solvent
  4. custompurify on an SCX cartridge
  5. washeluting with 2N ammonia/methanol
  6. customPurify further on a silica gel column
  7. washeluting with 0-10% methanol/methylene chloride

Sources & evidence

ORD record
ord-91e699f3885e4b4580d6983a531dace0
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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