Aluminium lithium hydride → Ospemifene

HRID 631767Notes

Reaction equation

HRID 631767 reaction equation
C([O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14](/[C:17](/[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:18](\[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)/[CH2:19][CH2:20][Cl:21])=[CH:13][CH:12]=1)(=O)C(C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1(C)C=CC=CC=1>[CH:25]1[CH:26]=[CH:27][C:22](/[C:18](/[CH2:19][CH2:20][Cl:21])=[C:17](\[C:14]2[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][OH:7])=[CH:12][CH:13]=2)/[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 90102187(Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl pivalate

Product 1

HCID 3036505OspemifeneYield 61.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl pivalate (3.5 g, 7.56 mmol) was dissolved in toluene (35 ml) and stirred under nitrogen for 5 min at room temperature. Lithium aluminium hydride solution (1 M in THF) (7.56 ml, 7.56 mmol) was added dropwise to the reaction and the mixture was stirred at room temperature for 30 min. After HPLC indicated completion, the reaction was quenched by addition of saturated NH4Cl-solution (75 ml). Additional amount of toluene (30 ml) was added and the phases were separated. The organic phase was washed with water (50 ml), brine (50 ml), dried (Na2SO4), filtered and concentrated in vacuo. The residue was crystallized froth 90% MeOH yielding ospemifene (1.75 g, 61%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. customthe reaction was quenched by addition of saturated NH4Cl-solution (75 ml)
  3. additionAdditional amount of toluene (30 ml) was added
  4. customthe phases were separated
  5. washThe organic phase was washed with water (50 ml), brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was crystallized froth 90% MeOH

Sources & evidence

ORD record
ord-429d578c5fa648558d95618bb378d0a2
Source dataset
uspto-grants-2016_04
Patent number
US09321712B2

Reaction notes

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