Tetrahydrofuran → Raloxifene

HRID 1649609Notes

Reaction equation

HRID 1649609 reaction equation
CS([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]S(C)(=O)=O)=[CH:33][CH:32]=3)[S:11][C:10]=2[CH:42]=1)(=O)=O.O1CCCC1.[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:42]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 993912284541-30-0

Product 1

HCID 5035Raloxifene

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 3.6 g. portion of 6-methanesulfonyloxy-2-(4-methanesulfonyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene was dissolved in 100 ml. of tetrahydrofuran and 40 ml. of methanol, and 10 ml. of 5 N sodium hydroxide was added. The mixture was stirred for 16 hours at ambient temperature, and was then worked up by the procedure of Example 3 above to obtain 3.5 g. of a yellow solid. The impure product was purified by column chromatography on silica gel, eluting with a gradient solvent from 5% methanol in chloroform to 30% methanol in chloroform. The product-containing fractions were evaporated to obtain 1.85 g. of oily product, which was recrystallized from acetone to obtain 1.25 g. of purified product, m.p. 141°-144° C.

Workup

  1. customto obtain 3.5 g
  2. customThe impure product was purified by column chromatography on silica gel
  3. washeluting with a gradient solvent from 5% methanol in chloroform to 30% methanol in chloroform
  4. customThe product-containing fractions were evaporated
  5. customto obtain 1.85 g
  6. customof oily product, which was recrystallized from acetone
  7. customto obtain 1.25 g

Sources & evidence

ORD record
ord-2136ca8961874f6abc75dbe0a9f0f175
Source dataset
uspto-grants-1983_11
Patent number
US04418068

Reaction notes

Loading…