Hydrochloric Acid → HCID 68515938, compound

HRID 732746Notes

Reaction equation

HRID 732746 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:21]C)[CH:17]=3)[C:12]=2[O:23][C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:26][CH:25]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].Cl.B(Br)(Br)Br.[Cl:44]CCl.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.C(OCC)C.CO>[ClH:44].[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[C:12]([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)=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH:17]=[C:16]([OH:21])[CH:15]=[CH:14]3)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 6344DichloromethaneHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 59751450HCID 59751450, compound

Product 1

HCID 68515938HCID 68515938, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
0 °C

Procedure

Dissolve the product of Example 15 in ethyl acetate (10 mL) and diethyl-ether (5 mL). Add 2M HCl in diethyl ether (1 mL, 2.0 mmol). Concentrate the slurry and dry in vacuo. Dilute the residue in dichloromethane (5.0 mL) and blanket with nitrogen. Cool the solution to 0° C. with an external ice bath and add 1M BBr3 in dichloromethane (1.0 mL, 1.0 mmol). After 20 minutes, dilute the reaction mixture with ethyl acetate (25.0 mL) and add saturated aqueous NaHCO3 in parts (2×10 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 6-(3-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol in dichloromethane (0 to 5%). Dissolve the free base in diethyl ether (5.0 mL), ethyl acetate (6.0 mL) and methanol (1.0 mL) and add 2M HCl in diethyl ether (1 mL, 2.0 mmol). Collect the precipitate on filter paper, rinse with diethyl ether and dry in vacuo (<2 mm of Hg) at 65° C. for 48 hours to give 73 mg of the title compound (26%): mass spectrum (ion spray): m/z=518.5 (M[free base]+1).

Workup

  1. concentrationConcentrate the slurry
  2. customdry in vacuo
  3. additionDilute the residue in dichloromethane (5.0 mL)
  4. customSeparate the layers
  5. washwash the organic layer with brine (10 mL)
  6. dry with materialdry with MgSO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. washChromatograph the residue on a SiO2 column eluting 6-(3-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol in dichloromethane (0 to 5%)
  10. dissolutionDissolve the free base in diethyl ether (5.0 mL)
  11. customCollect the precipitate
  12. filtrationon filter paper
  13. washrinse with diethyl ether
  14. customdry in vacuo (<2 mm of Hg) at 65° C. for 48 hours

Sources & evidence

ORD record
ord-0a835ac9abc14e2ba6b072c6b8ae9d67
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

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