Sodium Carbonate → 1-(2-{4-[6-Benzyloxy-2-(4-ethanesulfonyl-phenyl)-benzo[b]thiophen-3-yloxy]-phenoxy}-ethyl)-piperidine

HRID 732822Notes

Reaction equation

HRID 732822 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:17][C:18]3[CH:32]=[CH:31][C:21]([O:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)=[C:15](Br)[S:14][C:13]=2[CH:34]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:41]([S:43]([C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1)(=[O:45])=[O:44])[CH3:42]>O1CCOCC1.C(OCC)C.O.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>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:17][C:18]3[CH:32]=[CH:31][C:21]([O:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)=[C:15]([C:49]3[CH:48]=[CH:47][C:46]([S:43]([CH2:41][CH3:42])(=[O:45])=[O:44])=[CH:51][CH:50]=3)[S:14][C:13]=2[CH:34]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27734204-(Ethylsulphonyl)benzeneboronic acidHCID 690745451-{2-[4-(6-Benzyloxy-2-bromo-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine

Product 1

HCID 597514231-(2-{4-[6-Benzyloxy-2-(4-ethanesulfonyl-phenyl)-benzo[b]thiophen-3-yloxy]-phenoxy}-ethyl)-piperidineYield 49%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Dissolve 1-{2-[4-(6-benzyloxy-2-bromo-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine (700 mg, 1.3 mmol) in dioxane (13 mL) and 10% aqueous sodium carbonate (6.9 mL, 6.5 mmol) and add 4-(ethanesulphonyl)benzene boronic acid (430 mg, 2 mmol) and Pd(PPh3)4 (150 mg, 0.13 mmol). Heat to 70° C. and stir overnight. Dilute with diethyl ether (25 mL) and water (25 mL), filter through Celite, and separate layers. Extract the aqueous layer with diethyl ether (50 mL). Combine the organic layers and wash with water (50 mL) and brine (50 mL). Dry with sodium sulfate, filter, and concentrate in vacuo. Chromatograph residue on a SiO2 column eluting with methanol in dichloromethane (0 to 5%) to give 400 mg of the title compound (49%): mass spectrum (ion spray): m/z=628.3 (M+H).

Workup

  1. filtrationfilter through Celite
  2. customseparate layers
  3. extractionExtract the aqueous layer with diethyl ether (50 mL)
  4. washCombine the organic layers and wash with water (50 mL) and brine (50 mL)
  5. dry with materialDry with sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. washChromatograph residue on a SiO2 column eluting with methanol in dichloromethane (0 to 5%)

Sources & evidence

ORD record
ord-c5137fb549414285be44766091a0a205
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

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