Raloxifene → [6-[N-(4-Chlorophenyl)carbamoyl]-2-[4-[N-(4chlorophenyl)carbamoyl]phenyl]benzo[b]thien-3-yl][4-[2-(1piperidinyl)ethoxy]-phenyl]methanone

HRID 1954513Notes

Reaction equation

HRID 1954513 reaction equation
O[C:2]1[CH:3]=[CH:4][C:5]2[C:9]([C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[CH:14][CH:13]=3)=[O:11])=[C:8]([C:27]3[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=3)[S:7][C:6]=2[CH:34]=1.[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([N:42]=[C:43]=[O:44])=[CH:38][CH:37]=1>O1CCCC1>[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]([C:2]2[CH:3]=[CH:4][C:5]3[C:9]([C:10]([C:12]4[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][N:21]5[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]5)=[CH:16][CH:17]=4)=[O:11])=[C:8]([C:27]4[CH:28]=[CH:29][C:30]([C:43](=[O:44])[NH:42][C:39]5[CH:40]=[CH:41][C:36]([Cl:35])=[CH:37][CH:38]=5)=[CH:31][CH:32]=4)[S:7][C:6]=3[CH:34]=2)=[O:44])=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 5035RaloxifeneHCID 76934-Chlorophenyl Isocyanate

Product 1

HCID 18357247[6-[N-(4-Chlorophenyl)carbamoyl]-2-[4-[N-(4chlorophenyl)carbamoyl]phenyl]benzo[b]thien-3-yl][4-[2-(1piperidinyl)ethoxy]-phenyl]methanoneYield 50.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5.56 g (10.7 mmol) of [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone was dissolved in 200 ml of dry tetrahydrofuran and 5.45 g (35.2 mmol) of 4-chlorophenyl -isocynate was added. The reaction mixture was stirred at room temperature under an atmosphere of nitrogen. After 18 hours, the solvent was removed by evaporation in vacuo, and redissolved in chloroform. The chloroform solution was cooled to -20° C. for 24 hours and the precipitate formed was filtered off. The remaining solution was chromatographed (Waters Prep 500, HPLC) on a silica gel column, eluted with a linear gradient of chloroform ending with chloroform-methanol (19:1)(v/v). The desired fractions were determined by thin layer chromatography, combined and evaporated to dryness to afford 4.01 g of the title compound as a tan amorphous powder.

Workup

  1. customthe solvent was removed by evaporation in vacuo
  2. dissolutionredissolved in chloroform
  3. temperatureThe chloroform solution was cooled to -20° C. for 24 hours
  4. customthe precipitate formed
  5. filtrationwas filtered off
  6. customThe remaining solution was chromatographed (Waters Prep 500, HPLC) on a silica gel column
  7. washeluted with a linear gradient of chloroform ending with chloroform-methanol (19:1)(v/v)
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-da11bad8e301441ebcb49f1f2db4be2c
Source dataset
uspto-grants-2000_09
Patent number
US06121292

Reaction notes

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