Iodine → 5-(4-(2-tetrahydropyranyloxymethyl)phenyl)-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-ol

HRID 413674

Reaction equation

HRID 413674 reaction equation
[Mg].II.BrCCBr.[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1.[CH:23]1[C:33]2[CH2:32][CH2:31][C:30]3[CH:34]=[CH:35][CH:36]=[CH:37][C:29]=3[C:28](=[O:38])[C:27]=2[CH:26]=[CH:25][CH:24]=1.[Cl-].[NH4+]>O1CCCC1>[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:28]2([OH:38])[C:29]3[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=3[CH2:31][CH2:32][C:33]3[CH:23]=[CH:24][CH:25]=[CH:26][C:27]2=3)=[CH:18][CH:17]=1

Participants

8

Reactant 6

HCID 807IodineHCID 78391,2-DibromoethaneHCID 14589DibenzosuberoneHCID 25517Ammonium ChlorideHCID 5981682-[(4-Bromophenyl)methoxy]oxaneHCID 5462224Magnesium

Product 1

HCID 192613715-(4-(2-tetrahydropyranyloxymethyl)phenyl)-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-olYield 41.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A mixture of magnesium turnings (1.07 g, 0.044 mol) activated with iodine, 1,2-dibromoethane and tetrahydrofuran (40 ml) was kept under a nitrogen atmosphere, and a solution of 4-bromophenylmethyl tetrahydro-2-pyranyl ether (11.20 g, 0.041 mol) in tetrahydrofuran (40 ml) was added dropwise under stirring. The mixture was gently heated to reflux temperature, and heating was continued for 3 h. The mixture was cooled to room temperature, and a solution of 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one (6.86 g, 0.033 mol) in tetrahydrofuran (40 ml) was added dropwise. The mixture was heated at reflux temperature for 1 h, cooled and then poured into an ice-cold saturated solution of ammonium chloride (85 ml). The mixture was extracted with ether (120 ml and 2×70 ml), and the combined organic layers were washed with water (2×40 ml), brine (40 ml) and dried (MgSO4). The solvent was removed in vacuo and the oily residue (14.7 g) was purified by column chromatography on silica gel (200 g) using first benzene and then a mixture of dichloromethane and ethanol (9:1) as eluents. The dichloromethane/ethanol fraction afforded 5.5 g (41%) of 5-(4-(2-tetrahydropyranyloxymethyl)phenyl)-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-ol.

Workup

  1. temperatureThe mixture was gently heated
  2. temperatureto reflux temperature
  3. temperatureheating
  4. temperatureThe mixture was heated
  5. temperatureat reflux temperature for 1 h
  6. temperaturecooled
  7. extractionThe mixture was extracted with ether (120 ml and 2×70 ml)
  8. washthe combined organic layers were washed with water (2×40 ml), brine (40 ml)
  9. dry with materialdried (MgSO4)
  10. customThe solvent was removed in vacuo
  11. customthe oily residue (14.7 g) was purified by column chromatography on silica gel (200 g)
  12. additiona mixture of dichloromethane and ethanol (9:1) as eluents

Sources & evidence

ORD record
ord-dfc5f36e93d942dd9581118a455c639f
Source dataset
uspto-grants-2003_05
Patent number
US06569849B1

Linked notes

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