Hydrochloric Acid → HCID 68520258, compound

HRID 732811Notes

Reaction equation

HRID 732811 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:23]C)[CH:19]=3)[C:14]=2[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)[CH:5]=[C:6]([F:12])[C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[ClH:41].B(Br)(Br)Br>C(OC(=O)C)C.C(OCC)C>[ClH:41].[F:1][C:2]1[CH:3]=[C:4]([C:13]2[C:14]([O:25][C:26]3[CH:27]=[CH:28][C:29]([O:30][CH2:31][CH2:32][N:33]4[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]4)=[CH:39][CH:40]=3)=[C:15]3[C:20](=[CH:21][CH:22]=2)[CH:19]=[C:18]([OH:23])[CH:17]=[CH:16]3)[CH:5]=[C:6]([F:12])[C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 25134Boron tribromideHCID 59751436HCID 59751436, compound

Product 1

HCID 68520258HCID 68520258, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve the compound of Example 79 in ethylacetate (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 an 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 column eluting the 6-(3,5-difluoro-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) and ethyl acetate (6.0 mL). Add 2M HCl in diethyl ether (0.1 mL, 0.2 mmol). Collect the precipitate on filter paper and rinse with diethyl ether to give 31 mg of the title compound (20%): mass spectrum (ion spray): m/z: 554.3 (M+H−HCl).

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 column eluting the 6-(3,5-difluoro-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-1d9aca97319e40beb77223eabd52393f
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

Loading…