Hydrochloric Acid → HCID 68517394, compound

HRID 732767Notes

Reaction equation

HRID 732767 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([S:9]([CH3:12])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:23]C)[CH:19]=2)[C:14]=1[O:25][C:26]1[CH:40]=[CH:39][C:29]([O:30][CH2:31][CH2:32][N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:28][CH:27]=1.Cl.B(Br)(Br)Br.CO>C(OCC)(=O)C.C(OCC)C>[ClH:1].[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([S:9]([CH3:12])(=[O:10])=[O:11])[CH:5]=[CH:4][C:3]=1[C:13]1[C:14]([O:25][C:26]2[CH:40]=[CH:39][C:29]([O:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:28][CH:27]=2)=[C:15]2[C:20](=[CH:21][CH:22]=1)[CH:19]=[C:18]([OH:23])[CH:17]=[CH:16]2

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 887MethanolHCID 25134Boron tribromideHCID 59751433HCID 59751433, compound

Product 1

HCID 68517394HCID 68517394, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

Dissolve the product of Example 33 in ethyl acetate (10 mL) and diethyl ether (5 mL). Add 2M HCl in diethyl ether (0.5 mL, 1.0 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 external ice bath. Add BBr3 (0.1 mL, 1.1 mmol) and stir for 1 hour. Quench with water (1.0 mL) and dilute with 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 the 6-(2,3-dichloro-4-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol/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 (0.5 mL, 1.0 mmol). Collect the precipitate on filter paper, rinse with diethyl ether to give 38 mg of the title compound (30%): mass spectrum (ion spray): m/z=586.2.

Workup

  1. concentrationConcentrate the slurry
  2. customdry in vacuo
  3. additionDilute the residue in dichloromethane (5.0 mL)
  4. customQuench with water (1.0 mL)
  5. additiondilute with dichloromethane (10 mL)
  6. customSeparate the layers
  7. washwash the organic layer with saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  8. dry with materialDry with MgSO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. washChromatograph the residue on a SiO2 column eluting the 6-(2,3-dichloro-4-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol with a step gradient of methanol/dichloromethane (0 to 5%)
  12. dissolutionDissolve the free base in diethyl ether (5.0 mL)
  13. customCollect the precipitate
  14. filtrationon filter paper
  15. washrinse with diethyl ether

Sources & evidence

ORD record
ord-783434cc512b423ba31ec1d7996eb60e
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

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