Hydrochloric Acid → 5-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-6-(thiophen-2-yl)naphthalen-2-ol hydrochloride

HRID 445211Notes

Reaction equation

HRID 445211 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[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]=1)=[C:8]([C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)[CH:7]=[CH:6]2.[ClH:34].B(Br)(Br)Br>ClCCl.C(#N)C.O>[ClH:34].[N:21]1([CH2:20][CH2:19][O:18][C:17]2[CH:16]=[CH:15][C:14]([O:13][C:9]3[C:8]([C:29]4[S:30][CH:31]=[CH:32][CH:33]=4)=[CH:7][CH:6]=[C:5]4[C:10]=3[CH:11]=[CH:12][C:3]([OH:2])=[CH:4]4)=[CH:28][CH:27]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 25134Boron tribromideHCID 583385531-(2-(4-(6-Methoxy-2-(thiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine

Product 1

HCID 673090525-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-6-(thiophen-2-yl)naphthalen-2-ol hydrochlorideYield 54.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Dissolve 1-(2-(4-(6-methoxy-2-(thiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine (100 mg, 0.22 mmol) in dichloromethane and treat with HCl (1M in ether; 220 μL, 0.22 mmol). Concentrate in vacuo to give a yellow solid and add dichloromethane (7.3 mL). Cool the resulting solution to 0° C. and add boron tribromide (1M in dichloromethane; 870 μL, 0.87 mmol). Stir the resulting mixture at 0° C. for 2.5 hours. Quench the mixture with saturated aqueous sodium bicarbonate and allow to warm to room temperature. Separate the layers and extract the aqueous layer with 20% methanol in dichloromethane (10 mL×3). Dry combined organic layers (Na2SO4), filter and concentrate in vacuo to give a yellow residue. Purify the residue by silica gel flash chromatography to give an off-white foam. Suspend the foam in ACN and add HCL (5M in water; 1 mL). Freeze the resulting solution and lyophilize to obtain the title compound (50.5 mg, 0.12 mmol): mass spectrum (m/z): 446 (M+1-HCl).

Workup

  1. concentrationConcentrate in vacuo
  2. customto give a yellow solid
  3. customQuench the mixture with saturated aqueous sodium bicarbonate
  4. temperatureto warm to room temperature
  5. customSeparate the layers
  6. extractionextract the aqueous layer with 20% methanol in dichloromethane (10 mL×3)
  7. customDry
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customto give a yellow residue
  11. customPurify the residue by silica gel flash chromatography
  12. customto give an off-white foam

Sources & evidence

ORD record
ord-cda280496d0d468f9e03c9a700710d55
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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