Hydrochloric Acid → 1-{2-[4-(6-Benzyloxy-2-bromo-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine

HRID 748955Notes

Reaction equation

HRID 748955 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:17][C:18]3[CH:32]=[CH:31][C:21]([O:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)=[C:15]([Br:33])[S:14](=O)[C:13]=2[CH:35]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CO.C(Cl)(Cl)Cl.ClCCl.[Cl-].[Cl-].[Cl-].[Ti+3]>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:17][C:18]3[CH:32]=[CH:31][C:21]([O:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)=[C:15]([Br:33])[S:14][C:13]=2[CH:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 690747101-{2-[4-(6-benzyloxy-2-bromo-1-oxo-1H-1lambda4-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine

Product 1

HCID 690745451-{2-[4-(6-Benzyloxy-2-bromo-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidineYield 88.5%

Reagents, catalysts & solvents 4

HCID 10313229titanium(III) trichlorideCatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

Dissolve 1-{2-[4-(6-benzyloxy-2-bromo-1-oxo-1H-1λ4-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine (22.36 g, 40.3 mmol) in methanol (160 mL) and chloroform (80 mL). Add a 30% solution of titanium trichloride in aqueous HCl (31.4 mL, 80.6 mmol) and stir at ambient temperature for 2 hours. Quench reaction mixture with saturated aqueous sodium bicarbonate (500 mL) and dilute with dichloromethane (500 mL). Separate layers and wash the organic layer with saturated aqueous sodium bicarbonate (500 mL), water (500 mL), and brine (500 mL). Dry with sodium sulfate, filter and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting with methanol (containing 10% NH4OH) in dichloromethane (0 to 2%) to give 19.2 g of the title compound (88%).

Workup

  1. customQuench
  2. customreaction mixture with saturated aqueous sodium bicarbonate (500 mL)
  3. washSeparate layers and wash the organic layer with saturated aqueous sodium bicarbonate (500 mL), water (500 mL), and brine (500 mL)
  4. dry with materialDry with sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. washChromatograph the residue on a SiO2 column eluting with methanol (containing 10% NH4OH) in dichloromethane (0 to 2%)

Sources & evidence

ORD record
ord-13527932b7c647c3a1fc8a44f5e23d70
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

Loading…