Tetrahydrofuran → Raloxifene

HRID 2198613Notes

Reaction equation

HRID 2198613 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 24 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°.

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-d6f5126840d44adc80d23b4499b13e05
Source dataset
uspto-grants-1982_11
Patent number
US04358593

Reaction notes

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