Raloxifene → 6-Benzoyloxy-2-(4-benzoyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, hydrochloride

HRID 1649614Notes

Reaction equation

HRID 1649614 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([C:10](=[O:26])[C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[CH:13][CH:12]=3)=[C:8]([C:27]3[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=3)[S:7][C:6]=2[CH:34]=1.[C:35](=[O:38])([O-])[O-].[K+].[K+].[C:41]([Cl:49])(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.[Cl-].[Na+]>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[ClH:49].[C:41]([O:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([C:10](=[O:26])[C:11]3[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH2:19][N:20]4[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]4)=[CH:15][CH:16]=3)=[C:8]([C:27]3[CH:28]=[CH:29][C:30]([O:33][C:35](=[O:38])[C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:34]=4)=[CH:31][CH:32]=3)[S:7][C:6]=2[CH:34]=1)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 5035RaloxifeneHCID 5234Sodium ChlorideHCID 7412Benzoyl chlorideHCID 11430Potassium Carbonate

Product 1

HCID 1317128706-Benzoyloxy-2-(4-benzoyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, hydrochloride

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

A 2 g. portion of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]-thiophene was suspended in 35 ml. of chloroform, and 3.5 g. of potassium carbonate was added. The flask was blanketed with nitrogen, and 2 mg. of 4-dimethylaminopyridine and 1.2 g. of benzoyl chloride were added. The mixture was heated in an 80° C. oil bath for 4 hours under reflux, and was then poured into a large amount of aqueous sodium chloride solution. The mixture was then extracted three times with 50 ml. portions of chloroform, and the organic layers were combined and washed with aqueous sodium chloride solution and dried over magnesium sulfate. The solution was then filtered, and hydrogen chloride gas was bubbled through it. Solvent was then removed under vacuum, leaving a gray oil, which was triturated with denatured alcohol and seeded with an authentic sample of the desired product to obtain white crystals, which were washed with diethyl ether and recrystallized from dichloromethane/ethanol to obtain 1.86 g. of the desired product, m.p. 235°-236° C.

Workup

  1. temperatureunder reflux
  2. extractionThe mixture was then extracted three times with 50 ml
  3. washwashed with aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solution was then filtered
  6. customhydrogen chloride gas was bubbled through it
  7. customSolvent was then removed under vacuum
  8. customleaving a gray oil, which
  9. customwas triturated with denatured alcohol
  10. customto obtain white crystals, which
  11. washwere washed with diethyl ether
  12. customrecrystallized from dichloromethane/ethanol
  13. customto obtain 1.86 g

Sources & evidence

ORD record
ord-609fd9f7f9b44d21b16d5886cfc09c4b
Source dataset
uspto-grants-1983_11
Patent number
US04418068

Reaction notes

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