Cesium fluoride → 1-(2-{4-[2-(3,4-Difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-azepane

HRID 1513873Notes

Reaction equation

HRID 1513873 reaction equation
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[N:20]1([CH2:27][CH2:28][O:29][C:30]2[CH:56]=[CH:55][C:33]([O:34][C:35]3[C:44]4[C:39](=[CH:40][C:41]([O:45][CH3:46])=[CH:42][CH:43]=4)[CH:38]=[CH:37][C:36]=3OS(C(F)(F)F)(=O)=O)=[CH:32][CH:31]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.[F-].[Cs+].[F:59][C:60]1[CH:61]=[C:62](B(O)O)[CH:63]=[CH:64][C:65]=1[F:66]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Pd].C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C(#N)C>[F:59][C:60]1[CH:61]=[C:62]([C:36]2[CH:37]=[CH:38][C:39]3[C:44](=[CH:43][CH:42]=[C:41]([O:45][CH3:46])[CH:40]=3)[C:35]=2[O:34][C:33]2[CH:55]=[CH:56][C:30]([O:29][CH2:28][CH2:27][N:20]3[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]3)=[CH:31][CH:32]=2)[CH:63]=[CH:64][C:65]=1[F:66]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 27343373,4-Difluorobenzeneboronic acidHCID 57552539Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl ester

Product 1

HCID 111796201-(2-{4-[2-(3,4-Difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-azepaneYield 86%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 87307855Pd Pcy3CatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
90 °C

Procedure

Combine palladium acetate (33 mg, 0.15 mmol), tricyclohexyl phosphine (61 mg, 0.22 mmol) and acetonitrile (6 mL). Sonicate the mixture for 5 minutes. Combine trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl ester (787 mg, 1.46 mmol), cesium fluoride (2.00 g, 13.2 mmol), 3,4-difluorophenylboronic acid (692 mg, 4.38 mmol) and acetonitrile (16 mL). Add the sonicated Pd/Pcy3 suspension to reaction vessel and heat to 90° C. for 30 minutes. Cool to room temperature and filter through pad of Celite and evaporate the solvent. Dissolve residue in ethyl acetate (40 mL) and wash with saturated NaHCO3 (10 mL). Separate the layers, wash the organic layer with brine (10 ml), dry with MgSO4, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting the material with methanol in dichloromethane (0 to 5%) to give 630 mg (86%) of the title compound: mass spectrum (ion spray) m/z=504.2 (M+H).

Workup

  1. customSonicate the mixture for 5 minutes
  2. customto reaction vessel
  3. temperatureCool to room temperature
  4. filtrationfilter through pad of Celite
  5. customevaporate the solvent
  6. washDissolve residue in ethyl acetate (40 mL) and wash with saturated NaHCO3 (10 mL)
  7. customSeparate the layers
  8. washwash the organic layer with brine (10 ml)
  9. dry with materialdry with MgSO4
  10. filtrationfilter
  11. concentrationconcentrate in vacuo
  12. washChromatograph the residue on a SiO2 column eluting the material with methanol in dichloromethane (0 to 5%)

Sources & evidence

ORD record
ord-a4d79ef3669c4cf987e3fe9c7f44daf9
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…