Hydrochloric Acid → 6-(5-Methylthiophen-2-yl)-5-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ol

HRID 445201Notes

Reaction equation

HRID 445201 reaction equation
Cl.C[O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10]([O:14][C:15]1[CH:29]=[CH:28][C:18]([O:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:17][CH:16]=1)=[C:9]([C:30]1[S:31][C:32]([CH3:35])=[CH:33][CH:34]=1)[CH:8]=[CH:7]2.B(Br)(Br)Br.Cl>ClCCl.CO>[CH3:35][C:32]1[S:31][C:30]([C:9]2[C:10]([O:14][C:15]3[CH:29]=[CH:28][C:18]([O:19][CH2:20][CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)=[C:11]3[C:6](=[CH:7][CH:8]=2)[CH:5]=[C:4]([OH:3])[CH:13]=[CH:12]3)=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 25134Boron tribromide2×HCID 673080501-(2-(4-(6-Methoxy-2-(5-methylthiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine hydrochloride

Product 1

HCID 451026266-(5-Methylthiophen-2-yl)-5-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-olYield 97.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Dissolve 1-(2-(4-(6-methoxy-2-(5-methylthiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine hydrochloride (5.15 g, 10.1 mmol) in dichloromethane (340 mL). Cool the resulting solution to 0° C. In a separate container under nitrogen combine neat boron tribromide (3.9 mL, 40.4 mmol) and dichloromethane (36.5 mL). Add the resulting boron tribromide solution to the cooled solution. Stir the resulting mixture at 0° C. for 2.5 hours. Quench the mixture with saturated aqueous sodium bicarbonate and allow it to warm to room temperature. Separate the layers and extract the aqueous layer with 20% methanol in dichloromethane (10 mL×3). Concentrate the combined organic solutions to give a solid. Slurry the solid in methanol (234 mL) and add HCl (1N in water; 10.8 mL). Load the resulting solution onto an SCX acidic ion exchange column. Flush the column with 40% methanol in dichloromethane then elute desired material with 40% 7M ammonia in methanol in dichloromethane. Concentrate the ammonia containing eluent to give the title compound (4.54 g, 9.88 mmol). LRMS (m/z): 460 (M+1).

Workup

  1. customQuench the mixture with saturated aqueous sodium bicarbonate
  2. temperatureto warm to room temperature
  3. customSeparate the layers
  4. extractionextract the aqueous layer with 20% methanol in dichloromethane (10 mL×3)
  5. concentrationConcentrate the combined organic solutions
  6. customto give a solid
  7. customFlush the column with 40% methanol in dichloromethane
  8. washthen elute desired material with 40% 7M ammonia in methanol in dichloromethane
  9. concentrationConcentrate the ammonia containing eluent

Sources & evidence

ORD record
ord-fc3e2b0bee684886893e0407ba759dda
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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