Sodium ethanethiolate → 6-Benzo[b]thiophen-5-yl-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol

HRID 748914Notes

Reaction equation

HRID 748914 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([O:20]C)[CH:16]=4)[C:11]=3[O:22][C:23]3[CH:37]=[CH:36][C:26]([O:27][CH2:28][CH2:29][N:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:25][CH:24]=3)[CH:8]=[CH:9][C:2]1=2.C([S-])C.[Na+]>CN(C)C=O>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([C:10]3[C:11]([O:22][C:23]4[CH:24]=[CH:25][C:26]([O:27][CH2:28][CH2:29][N:30]5[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]5)=[CH:36][CH:37]=4)=[C:12]4[C:17](=[CH:18][CH:19]=3)[CH:16]=[C:15]([OH:20])[CH:14]=[CH:13]4)[CH:8]=[CH:9][C:2]1=2

Participants

4

Reactant 2

HCID 4459711Sodium ethanethiolateHCID 59751440HCID 59751440, compound

Product 1

HCID 685144076-Benzo[b]thiophen-5-yl-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-olYield 58.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

Dissolve the compound of Example 50 (240 mg, 0.48 mmol) in dimethylformamide (DMF, 7 mL), add sodium ethanethiolate (EtSNa, 100 mg, 1.19 mmol). Flush the flask with N2 and then heat the reaction mixture to 150° C. Continue to heat the reaction mixture for 0.5 hours, cool to room temperature. Add water (15 mL), and extract the aqueous layer with CH2Cl2 (3×15 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 0-8% MeOH—NH4OH (10/1, v/v) in CH2Cl2) to give 140 mg of crude 6-benzo[b]thiophen-5-yl-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol. Purify the impure product by preparative HPLC (Gilson) to give 95 mg of the title compound (55%): mass spectrum (ion spray): m/z=496.3 (M+H-TFA).

Workup

  1. customFlush the flask with N2
  2. temperatureto heat the reaction mixture for 0.5 hours
  3. temperaturecool to room temperature
  4. extractionAdd water (15 mL), and extract the aqueous layer with CH2Cl2 (3×15 mL)
  5. dry with materialCombine the organic layers and dry with Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. custompurify by flash column chromatography (silica gel, 0-8% MeOH—NH4OH (10/1

Sources & evidence

ORD record
ord-b37c46e2079c413783053ba6f7a48c7d
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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