Hydrochloric Acid → 8-Fluoro-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-thia-chrysen-2-ol hydrochloride

HRID 1513978Notes

Reaction equation

HRID 1513978 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[C:16]1[C:7](=[C:8]3[C:13](=[CH:14][CH:15]=1)[CH:12]=[C:11]([O:20]C)[CH:10]=[CH:9]3)[CH:6]([C:22]1[CH:36]=[CH:35][C:25]([O:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:24][CH:23]=1)[S:5]2.[ClH:37].CC(=CC)C.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CCOCC>[ClH:37].[F:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[C:16]1[C:7](=[C:8]3[C:13](=[CH:14][CH:15]=1)[CH:12]=[C:11]([OH:20])[CH:10]=[CH:9]3)[CH:6]([C:22]1[CH:23]=[CH:24][C:25]([O:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)=[CH:35][CH:36]=1)[S:5]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 114548221-{2-[4-(8-Fluoro-2-methoxy-5H-6-thia-chrysen-5-yl)-phenoxy]-ethyl}-piperidine

Product 1

HCID 670048228-Fluoro-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-thia-chrysen-2-ol hydrochlorideYield 65%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Dissolve 1-{2-[4-(8-fluoro-2-methoxy-5H-6-thia-chrysen-5-yl)-phenoxy]-ethyl}-piperidine (330 mg, 0.67 mmol) in methylene chloride (6.0 mL) and add 2M HCl in ether (0.67 mL). Concentrate in vacuo and dissolve in dry methylene chloride (6.0 mL). Add 2-methyl-2-butene (0.71 mL, 6.7 mmol) and cool to 0° C. under nitrogen. Add boron tribromide (0.25 mL, 2.7 mmol) slowly and stir at 0° C. for 20 minutes. Pour the reaction into saturated aqueous sodium bicarbonate and extract with methylene chloride/methanol (4:1). Dry organic layer with sodium sulfate, filter and concentrate in vacuo. Purify the resultant oil over silica gel (0% to 3% methanol in methylene chloride). Dissolve the resultant oil in methylene chloride (3 mL) and add 2M HCl in ether (0.5 mL). Remove the solvent in vacuo and place in a 50° C. vacuum oven overnight to yield 225 mg (65%) of the title compound: mass spectrum (ion spray) m/z=486.3 (M−Cl).

Workup

  1. concentrationConcentrate in vacuo
  2. dissolutiondissolve in dry methylene chloride (6.0 mL)
  3. additionPour
  4. extractionextract with methylene chloride/methanol (4:1)
  5. filtrationDry organic layer with sodium sulfate, filter
  6. concentrationconcentrate in vacuo
  7. customPurify the resultant oil over silica gel (0% to 3% methanol in methylene chloride)
  8. dissolutionDissolve the resultant oil in methylene chloride (3 mL)
  9. additionadd 2M HCl in ether (0.5 mL)
  10. customRemove the solvent in vacuo and place in a 50° C. vacuum oven overnight

Sources & evidence

ORD record
ord-a04970c350e349ff86415ee08ce70627
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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