Hydrochloric Acid → HCID 68519802, compound

HRID 748913Notes

Reaction equation

HRID 748913 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:10]2[C:11]([O:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:24][CH:23]=3)=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([OH:20])[CH:14]=[CH:13]3)[CH:5]=[CH:6][C:7]=1[S:8][CH3:9].B(O[O-])=[O:38].[Na+].[ClH:42].C(OCC)C.[OH2:48]>C(O)(=O)C.CO.C(OCC)(=O)C.ClCCl>[ClH:42].[CH3:9][S:8]([C:7]1[CH:6]=[CH:5][C:4]([C:10]2[C:11]([O:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:24][CH:23]=3)=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([OH:20])[CH:14]=[CH:13]3)=[CH:3][C:2]=1[CH3:1])(=[O:38])=[O:48]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 3283Diethyl EtherHCID 517072Sodium PerborateHCID 68519548HCID 68519548, compound

Product 1

HCID 68519802HCID 68519802, compoundYield 11%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine the compound of Example 48 and sodium perborate (162 mg, 1.62 mmol) in acetic acid (4 mL). After 2 days, add dichloromethane (20 mL) and water (5 mL). Separate the layers, wash the organic layer with saturated aqueous NaHCO3 (10 mL), brine (10 mL), dry with MgSO4, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting the 6-(4-methanesulfonyl-3-methyl-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 40 mg of the title compound (11%): mass spectrum (ion spray): m/z=537.0 (M+H—HCl).

Workup

  1. customSeparate the layers
  2. washwash the organic layer with saturated aqueous NaHCO3 (10 mL), brine (10 mL)
  3. dry with materialdry with MgSO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. washChromatograph the residue on a SiO2 column eluting the 6-(4-methanesulfonyl-3-methyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol in dichloromethane (0 to 5%)
  7. dissolutionDissolve the free base in diethyl ether (5.0 mL)
  8. customCollect the precipitate
  9. filtrationon filter paper
  10. washrinse with diethyl ether
  11. customdry in vacuo (<2 mm of Hg) at 65° C. for 48 hours

Sources & evidence

ORD record
ord-dcb150fbb89b47279d64d1bb4553d49e
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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