Iodine → 1-[2-(Dimethylamino)-1-[4-(phenylmethoxy)phenyl]ethyl]cyclohexanol

HRID 1472972Notes

Reaction equation

HRID 1472972 reaction equation
[Mg].II.Br[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]Br.CO[C:13](=[O:33])[CH:14]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)[CH2:15][N:16]([CH3:18])[CH3:17]>C(OCC)C>[CH2:26]([O:25][C:22]1[CH:21]=[CH:20][C:19]([CH:14]([C:13]2([OH:33])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]2)[CH2:15][N:16]([CH3:17])[CH3:18])=[CH:24][CH:23]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 807IodineHCID 81001,5-DibromopentaneHCID 5462224MagnesiumHCID 49872954HCID 49872954, compound

Product 1

HCID 201299231-[2-(Dimethylamino)-1-[4-(phenylmethoxy)phenyl]ethyl]cyclohexanol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
2.5 °C

Procedure

Activated magnesium turnings (8 g) and a few crystals of iodine were charged to diethyl ether (200 ml). After addition of 1,5-dibromopentane (20.7 ml; 0.15 mol), the reaction mixture was refluxed for 2 hours. The reaction mass was cooled to 0-5° C. Separately prepared solution of 2-(4-benzyloxy-phenyl)-3-dimethylamino-propionic acid methyl ester (10 g; 0.032 mol) in diethyl ether (100 ml) was added to the above reaction mass very slowly. The temperature was raised to 25-30° C. with constant stirring for 2 hours. After completion of the reaction; the reaction mass was quenched with saturated ammonium chloride solution (100 ml). The aqueous layer was extracted with ethyl acetate (2×50 ml) and the combined organic layer was washed with water (100 ml). The organic layer was dried on sodium sulphate, concentrated under reduced pressure and the product was isolated in n-heptane (25-30 ml). The material was dried under vacuum at 45-50° C. Yield: 7 g, Efficiency: 62%.

Workup

  1. temperaturethe reaction mixture was refluxed for 2 hours
  2. temperatureThe temperature was raised to 25-30° C.
  3. customAfter completion of the reaction
  4. customthe reaction mass was quenched with saturated ammonium chloride solution (100 ml)
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×50 ml)
  6. washthe combined organic layer was washed with water (100 ml)
  7. customThe organic layer was dried on sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customthe product was isolated in n-heptane (25-30 ml)
  10. customThe material was dried under vacuum at 45-50° C

Sources & evidence

ORD record
ord-550aa214b5664c4a99ec5acd85491f83
Source dataset
uspto-grants-2015_04
Patent number
US09012689B2

Reaction notes

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