Sodium Hydroxide → Raloxifene

HRID 2086004Notes

Reaction equation

HRID 2086004 reaction equation
Cl.CS([O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15](=[O:31])[C:16]3[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:18][CH:17]=3)=[C:13]([C:32]3[CH:37]=[CH:36][C:35]([O:38]S(C)(=O)=O)=[CH:34][CH:33]=3)[S:12][C:11]=2[CH:43]=1)(=O)=O.[OH-].[Na+]>CC(C)=O>[OH:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15](=[O:31])[C:16]3[CH:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]4)=[CH:20][CH:21]=3)=[C:13]([C:32]3[CH:33]=[CH:34][C:35]([OH:38])=[CH:36][CH:37]=3)[S:12][C:11]=2[CH:43]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 19603580(6-((Methylsulfonyl)oxy)-2-(4-((methylsulfonyl)oxy)phenyl)benzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)-, hydrochloride

Product 1

HCID 5035Raloxifene

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A 4 g. portion of 6-methanesulfonyloxy-2-(4-methanesulfonyloxyphenyl)-3-[4-(2-piperidinoethoxy)-benzoyl]benzo[b]thiophene, hydrochloride, was combined with 100 ml. of denatured alcohol and 10 ml. of 5 N sodium hydroxide, and stirred under reflux for 1.5 hours under a nitrogen atmosphere. The reaction mixture was then evaporated to dryness under vacuum, and the residue was dissolved in 200 ml. of water and washed with 300 ml. of diethyl ether. The water layer was degassed under vacuum, and then nitrogen was bubbled through it to remove all traces of ether. The mixture was then acidified with 1 N hydrochloric acid, and then made basic with excess sodium bicarbonate. The precipitate was collected by filtration and washed with cold water to obtain 2.4 g. of crude product. It was purified on a 2×30 cm. column of silica gel, eluting first with 700 ml. of 55 methanol in chloroform, followed by 1 liter of 10% methanol in chloroform. The impurities came off first, and the product-containing fractions were combined and evaporated under vacuum to obtain 1.78 g. of yellow oil. The oil was dissolved in 6 ml of acetone, seeded and chilled in a freezer to obtain 1.2 g. of purified product, m.p. 143°-147° C. The identity of the product was confirmed as follows:

Workup

  1. temperatureunder reflux for 1.5 hours under a nitrogen atmosphere
  2. customThe reaction mixture was then evaporated to dryness under vacuum
  3. dissolutionthe residue was dissolved in 200 ml
  4. washof water and washed with 300 ml
  5. customThe water layer was degassed under vacuum
  6. customnitrogen was bubbled through it
  7. customto remove all traces of ether
  8. filtrationThe precipitate was collected by filtration
  9. washwashed with cold water
  10. customto obtain 2.4 g
  11. customIt was purified on a 2×30 cm
  12. washcolumn of silica gel, eluting first with 700 ml
  13. customevaporated under vacuum
  14. customto obtain 1.78 g
  15. temperaturechilled in a freezer
  16. customto obtain 1.2 g

Sources & evidence

ORD record
ord-b63666ea046a4595912acf234bc0e9b9
Source dataset
uspto-grants-2004_04
Patent number
US06723739B1

Reaction notes

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