Sodium Hydroxide → Raloxifene

HRID 1649610Notes

Reaction equation

HRID 1649610 reaction equation
Cl.C([O:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([C:14](=[O:30])[C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)=[CH:17][CH:16]=3)=[C:12]([C:31]3[CH:36]=[CH:35][C:34]([O:37]C(=O)C)=[CH:33][CH:32]=3)[S:11][C:10]=2[CH:41]=1)(=O)C.[OH-].[Na+]>CO>[OH:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([C:14](=[O:30])[C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]4)=[CH:19][CH:20]=3)=[C:12]([C:31]3[CH:32]=[CH:33][C:34]([OH:37])=[CH:35][CH:36]=3)[S:11][C:10]=2[CH:41]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67811991HCID 67811991, compound2×

Product 1

HCID 5035Raloxifene

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The oily product of Example 1 above, 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, hydrochloride, was dissolved in 700 ml. of methanol and 100 ml. of 5 N sodium hydroxide. The mixture was stirred at ambient temperature for two hours, and was then evaporated to an oil under vacuum at a temperature below 40° C. The residue was dissolved in 500 ml. of water and washed twice with 500 ml. portions of diethyl ether. The aqueous layer was acidified to pH 2 with cold 50% aqueous methanesulfonic acid, diluted to about 3 liters, and washed twice with 1 liter portions of diethyl ether. The aqueous layer was then separated, thoroughly degassed under vacuum, and made basic with aqueous ammonia. The resulting solids were collected by filtration and vacuum dried at 40° C. to obtain 14.2 g. of crude product which was chromatographed over a 5×5 cm. column of Activity I silica gel, eluting with 15% methanol in chloroform. The product-containing fractions were evaporated to dryness to obtain a yellow foam, which was recrystallized from acetone to obtain 11.9 g. of product, which was substantially identical to the product of Example 3 above by nmr, ultraviolet and infrared analysis.

Workup

  1. customwas then evaporated to an oil under vacuum at a temperature below 40° C
  2. dissolutionThe residue was dissolved in 500 ml
  3. washof water and washed twice with 500 ml
  4. additiondiluted to about 3 liters
  5. washwashed twice with 1 liter portions of diethyl ether
  6. customThe aqueous layer was then separated
  7. customthoroughly degassed under vacuum
  8. filtrationThe resulting solids were collected by filtration and vacuum
  9. customdried at 40° C.
  10. customto obtain 14.2 g
  11. customof crude product which was chromatographed over a 5×5 cm
  12. washcolumn of Activity I silica gel, eluting with 15% methanol in chloroform
  13. customThe product-containing fractions were evaporated to dryness
  14. customto obtain a yellow foam, which
  15. customwas recrystallized from acetone
  16. customto obtain 11.9 g

Sources & evidence

ORD record
ord-b5a642719c7247eca507c821a468f308
Source dataset
uspto-grants-1983_11
Patent number
US04418068

Reaction notes

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