Cesium fluoride → 1-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-2-(4-cyclopropanesulfonylphenyl)-6-methoxy-naphthalene

HRID 748971Notes

Reaction equation

HRID 748971 reaction equation
[CH:1]1(S(C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)(=O)=O)C[CH2:2]1.[CH2:22]([O:29][C:30]1[CH:31]=[CH:32][C:33]2[C:37]([O:38][C:39]3[CH:53]=[CH:52][C:42]([O:43][CH2:44][CH2:45][N:46]4[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]4)=[CH:41][CH:40]=3)=[C:36]([C:54]3[CH:59]=[CH:58][C:57]([S:60]([CH3:63])(=[O:62])=[O:61])=[C:56](F)[CH:55]=3)S[C:34]=2[CH:65]=1)C1C=CC=CC=1.[F-].[Cs+].[CH:68]1(P(C2CCCCC2)C2CCCCC2)CCCC[CH2:69]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[N:46]1([CH2:45][CH2:44][O:43][C:42]2[CH:41]=[CH:40][C:39]([O:38][C:37]3[C:33]4[C:34](=[CH:65][C:30]([O:29][CH3:22])=[CH:31][CH:32]=4)[CH:2]=[CH:1][C:36]=3[C:54]3[CH:55]=[CH:56][C:57]([S:60]([CH:63]4[CH2:69][CH2:68]4)(=[O:62])=[O:61])=[CH:58][CH:59]=3)=[CH:53][CH:52]=2)[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 59751449(2-{4-[6-Benzyloxy-2-(3-fluoro-4-methanesulfonyl-phenyl)-benzo[b]thiophen-3-yloxy]-phenoxy}-ethyl)-piperidineHCID 685156112-(4-(Cyclopropylsulfonyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 104377421-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-2-(4-cyclopropanesulfonylphenyl)-6-methoxy-naphthaleneYield 512.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Combine 2-(4-cyclopropanesulfonyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (200 mg, 0.65 mmol), the compound of Preparation 1 (150 mg, 0.28 mmol) and cesium fluoride (214 mg, 1.4 mmol) in dried flask fitted with a reflux condenser. In a separate flask combine palladium (II) acetate (6.2 mg, 0.028 mmol) and tricyclohexylphosphine (11.7 mg, 0.042 mmol). Add acetonitrile (3.0 mL) and sonicate for 10 minutes under nitrogen. Add the catalyst solution to the solids and heat in an 80° C. oil bath for 20 minutes. Cool the suspension to room temperature and filter through packed celite. Rinse the celite with acetonitrile and evaporate. Chromatograph the residue on a SiO2 column eluting the material with methanol in dichloromethane (0 to 5%) to give 120 mg of the title compound (77%). Mass spectrum (ion spray): m/z 558.3 (M+H).

Workup

  1. customfitted with a reflux condenser
  2. customIn a separate flask combine
  3. additionAdd the catalyst solution to the solids
  4. temperatureCool the suspension to room temperature
  5. filtrationfilter
  6. washRinse the celite with acetonitrile
  7. customevaporate
  8. washChromatograph the residue on a SiO2 column eluting the material with methanol in dichloromethane (0 to 5%)

Sources & evidence

ORD record
ord-a3e1800a15014171b4e0f83c84520682
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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