Hydrochloric Acid → HCID 68518353, compound

HRID 748901Notes

Reaction equation

HRID 748901 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([CH3:37])=[C:12]([C:29]2[CH:34]=[CH:33][C:32]([O:35]C)=[CH:31][CH:30]=2)[O:13][C:14]2[CH:28]=[CH:27][C:17]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:16][CH:15]=2)=[CH:7][C:6]=1[C:38]([F:41])([F:40])[F:39])(=[O:4])=[O:3].[ClH:42].B(Br)(Br)Br.[CH3:47]O>C(OCC)(=O)C.C(OCC)C.O.ClCCl>[ClH:42].[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([O:13][C:14]3[CH:15]=[CH:16][C:17]([O:18][CH2:19][CH2:20][N:21]4[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]4)=[CH:27][CH:28]=3)=[C:29]3[C:34](=[CH:47][CH:37]=2)[CH:33]=[C:32]([OH:35])[CH:31]=[CH:30]3)=[CH:7][C:6]=1[C:38]([F:40])([F:41])[F:39])(=[O:4])=[O:3]

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 887MethanolHCID 25134Boron tribromideHCID 69073218HCID 69073218, compound

Product 1

HCID 68518353HCID 68518353, compoundYield 53%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

Dissolve the product of Example 31 in ethyl acetate (10 mL) and diethyl ether (5 mL). Add 2M HCl in diethyl ether (0.1 mL, 0.2 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 external ice bath. Add BBr3 (0.1 mL, 1.1 mmol) and stir for 1 hour. Dilute with water (1.0 mL) and dichloromethane (10 mL). Separate the layers and wash the organic layer with saturated aqueous NaHCO3 (10 mL) and brine (10 mL). Dry with MgSO4, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting the 6-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol/dichloromethane (O 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 (0.1 mL, 0.2 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 34 mg of the title compound (53%).

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 saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  6. dry with materialDry with MgSO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. washChromatograph the residue on a SiO2 column eluting the 6-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol/dichloromethane (O 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-fd72facb45c248c393cf42fd1e103781
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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