Hydrochloric Acid → HCID 68520285, compound

HRID 732749Notes

Reaction equation

HRID 732749 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:22]C)[CH:18]=3)[C:13]=2[O:24][C:25]2[CH:39]=[CH:38][C:28]([O:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:27][CH:26]=2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[ClH:40].B(Br)(Br)Br>C(OCC)(=O)C.C(OCC)C.CO.ClCCl.O>[ClH:40].[F:1][C:2]1[CH:3]=[C:4]([C:12]2[C:13]([O:24][C:25]3[CH:39]=[CH:38][C:28]([O:29][CH2:30][CH2:31][N:32]4[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]4)=[CH:27][CH:26]=3)=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([OH:22])[CH:16]=[CH:15]3)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

9

Reactant 3

HCID 313Hydrochloric Acid2×HCID 25134Boron tribromideHCID 59751422HCID 59751422, compound

Product 1

HCID 68520285HCID 68520285, compoundYield 26%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

Dissolve the product of Example 17 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. Add 1M BBr3 in dichloromethane (0.1 mL, 1.1 mmol) and stir for 1 hour. Add water (1.0 mL) and dichloromethane (10 mL). Separate the layers, 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 6-(3-fluoro-4-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 19 mg of the title compound (26%): mass spectrum (ion spray): m/z=536.3 (M+H).

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 6-(3-fluoro-4-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-32e5ae74fbbe4731b2a2c8f03cd7064e
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

Loading…