4-[2-(Piperidin-1-yl)ethoxy]phenol → 1-{2-[4-(6-benzyloxy-2-bromo-1-oxo-1H-1lambda4-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine

HRID 748954Notes

Reaction equation

HRID 748954 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16](Br)=[C:15]([Br:18])[S:14](=[O:19])[C:13]=2[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:21]1([CH2:27][CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.CC(C)([O-])C.[K+]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:36][C:33]3[CH:32]=[CH:31][C:30]([O:29][CH2:28][CH2:27][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[CH:35][CH:34]=3)=[C:15]([Br:18])[S:14](=[O:19])[C:13]=2[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 106090214-[2-(Piperidin-1-yl)ethoxy]phenolHCID 23665647Potassium tert-butoxideHCID 690700516-Benzyloxy-2,3-dibromo-benzo[b]thiophene 1-oxide

Product 1

HCID 690747101-{2-[4-(6-benzyloxy-2-bromo-1-oxo-1H-1lambda4-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidineYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
45 °C

Procedure

Dissolve 6-benzyloxy-2,3-dibromo-benzo[b]thiophene 1-oxide (5.9 g, 14.2 mmol) in THF (120 mL). Add a suspension of 4-(2-piperidin-1-yl-ethoxy)-phenol (3.14 g, 14.2 mmol) and potassium tert-butoxide (1.75 g, 15.6 mmol) in THF (120 mL) and stir at 45° C. for 1 hour. Partition reaction mixture between dichloromethane (400 mL) and saturated aqueous NH4Cl (400 mL) and separate. Wash the organic layer with saturated aqueous NH4Cl (400 mL) and brine. Dry with sodium sulfate, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting with methanol in dichloromethane (0 to 5%) to give 6.9 g of 1-{2-[4-(6-benzyloxy-2-bromo-1-oxo-1H-1λ4-benzo[b]thiophen-3-yloxy)-phenoxy]-ethyl}-piperidine (88%).

Workup

  1. additionAdd
  2. customPartition
  3. customreaction mixture between dichloromethane (400 mL) and saturated aqueous NH4Cl (400 mL)
  4. customseparate
  5. washWash the organic layer with saturated aqueous NH4Cl (400 mL) and brine
  6. dry with materialDry with sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. washChromatograph the residue on a SiO2 column eluting with methanol in dichloromethane (0 to 5%)

Sources & evidence

ORD record
ord-1da6cbf5b9ff41f2ada7db9f7895c789
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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