Hydrochloric Acid → HCID 68514417, compound

HRID 732753Notes

Reaction equation

HRID 732753 reaction equation
[O:1]=[S:2]1(=[O:39])[CH2:6][CH2:5][C:4]2[CH:7]=[C:8]([C:11]3[CH:20]=[CH:19][C:18]4[C:13](=[CH:14][CH:15]=[C:16]([O:21]C)[CH:17]=4)[C:12]=3[O:23][C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:26][CH:25]=3)[CH:9]=[CH:10][C:3]1=2.Cl.B(Br)(Br)Br.O>C(Cl)Cl>[O:39]=[S:2]1(=[O:1])[CH2:6][CH2:5][C:4]2[CH:7]=[C:8]([C:11]3[C:12]([O:23][C:24]4[CH:25]=[CH:26][C:27]([O:28][CH2:29][CH2:30][N:31]5[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]5)=[CH:37][CH:38]=4)=[C:13]4[C:18](=[CH:19][CH:20]=3)[CH:17]=[C:16]([OH:21])[CH:15]=[CH:14]4)[CH:9]=[CH:10][C:3]1=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 25134Boron tribromideHCID 59751434HCID 59751434, compound

Product 1

HCID 68514417HCID 68514417, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve the compound of Example 22 (160 mg, 0.29 mmol) in CH2Cl2 (5 mL) and cool the solution to −78° C. Add HCl (0.2 mL, 2.0 M in diethyl ether (Et2O)) and stir the reaction mixture for 10 minutes. Remove the solvent under reduced pressure and then dissolve the solid in CH2Cl2 (5 mL) under N2. Cool the solution to 0° C. and add BBr3 (370 mg, 1.46 mmol). Stir the reaction for one hour and add water (20 mL). Extract the aqueous layer with CH2Cl2 (3×20 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 2-8% MeOH—NH4OH (10/1, v/v)/CH2Cl2) to give 6-(1,1-dioxo-2,3-dihydro-1H-1λ6-benzo[b]thiophen-5-yl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol. Dissolve the free base in CH2Cl2 (5 mL) and cool to −78° C. Add HCl (0.5 mL, 2.0 M in Et2O) and stir the solution for 10 minutes. Remove the solvent under reduced pressure to give a solid. Dry the solid at 40° C., overnight, in vacuo to give 42 mg of the title compound (27%): mass spectrum (ion spray): m/z=530.3 (M+H).

Workup

  1. customRemove the solvent under reduced pressure
  2. dissolutiondissolve the solid in CH2Cl2 (5 mL) under N2
  3. temperatureCool the solution to 0° C.
  4. customthe reaction for one hour
  5. extractionExtract the aqueous layer with CH2Cl2 (3×20 mL)
  6. dry with materialCombine the organic layers and dry with Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify by flash column chromatography (silica gel, 2-8% MeOH—NH4OH (10/1

Sources & evidence

ORD record
ord-f384ed374b1343a5a3d3e3c147ba47b5
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

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