Methanol → Ospemifene

HRID 631766Notes

Reaction equation

HRID 631766 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.CO.O.[OH-].[Na+]>C1COCC1>[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

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 90102187(Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl pivalate

Product 1

HCID 3036505OspemifeneYield 35.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl pivalate (1 g, 2.16 mmol) was dissolved in THF (8 ml) followed by addition of MeOH (1 ml) and water (1 ml). Sodium hydroxide (0.1 g, 2.5 mmol) was added in one portion and the reaction was stirred at room temperature for 12 h. After completion of the reaction the mixture was partitioned between water (20 ml) and EtOAc (20 ml). Organic phase was washed with water (20 ml) and brine (20 ml), dried (Na2SO4), filtered and concentrated. The residue was crystallized from i-PrOH yielding ospemifene (0.29 g, 35%) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.37 (2H, t, J=8 Hz, ArH), 7.29 (3H, t, J=7.2 Hz, ArH), 7.20 (2H, t, J=7.6 Hz, ArH), 7.16-7.13 (3H, m, ArH), 6.80 (2H, d, J=8.8 Hz, ArH), 6.57 (2H, d, J=8.8 Hz, ArH), 3.94 (2H, t, J=4.4 Hz, ArOCH2CH2OH), 3.87 (2H, m, ArOCH2CH2OH), 3.42 (2H, t, J=7.2 Hz, ClCH2CH2), 2.92 (2H, t, J=7.2 Hz, ClCH2CH2), 1.95 (1H, t, J=6.4 Hz, OH). 13C-NMR (100 MHz, CDCl3) δ (ppm): 157.2, 143.2, 142.1, 141.3, 2×135.7, 132.2, 130.0, 129.8, 128.8, 128.7, 127.4, 127.0, 113.9, 69.3, 61.8, 43.3, 39.0.

Workup

  1. customAfter completion of the reaction the mixture
  2. customwas partitioned between water (20 ml) and EtOAc (20 ml)
  3. washOrganic phase was washed with water (20 ml) and brine (20 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was crystallized from i-PrOH

Sources & evidence

ORD record
ord-3f30148b88724bbcb2e6c284308b2fb5
Source dataset
uspto-grants-2016_04
Patent number
US09321712B2

Reaction notes

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