Triethylamine → 4'-tert-Butyldimethylsilyl-6-hydroxy Raloxifene

HRID 1387008Notes

Reaction equation

Cl.[N:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:20]4[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][C:21]=4[S:22][C:23]=3[C:24]3[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=3)=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[C:43]([Si:47](Cl)([CH3:49])[CH3:48])([CH3:46])([CH3:45])[CH3:44]>C1COCC1.CN(C=O)C.C1(C)C=CC=CC=1>[N:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:20]4[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][C:21]=4[S:22][C:23]=3[C:24]3[CH:29]=[CH:28][C:27]([O:30][Si:47]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:49])[CH3:48])=[CH:26][CH:25]=3)=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 30 g (58.8 mmol) of 6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl 4-[2-(1-piperidinyl)ethoxy]phenyl ketone hydrochloride in 120 mL of anhydrous THF and 60 mL of anhydrous DMF was added 20 mL (144 mmol) of anhydrous triethylamine and 9.75 g (64.7 mmol) of tertbutyldimethylsilyl chloride under a nitrogen atmosphere. The reaction mixture was heated at 60° C. in an oil bath for 4 h and then cooled to room temperature. The solution was diluted with 225 mL of toluene, filtered through a medium glass frit, and concentrated at reduced pressure. The residue was purified by PrepLC (0 to 4% MeOH in CH2Cl2) to give 6.77 g (11.5 mmol, 20%) of a yellow foam.

Workup

temperaturecooled to room temperature
filtrationfiltered through a medium glass frit
concentrationconcentrated at reduced pressure
customThe residue was purified by PrepLC (0 to 4% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-34199ebe93e14df6b8c0b9981e0ebb71
Source dataset: uspto-grants-2001_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06265575B1

Reaction notes

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