Hydrochloric Acid → Raloxifene Hydrochloride

HRID 1799520Notes

Reaction equation

[CH:1]1[C:6]([C:7]2[S:15][C:14]3[CH:13]=[C:12]([OH:16])[CH:11]=[CH:10][C:9]=3[C:8]=2[C:17]([C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:23][CH:24]=2)=[O:18])=[CH:5][CH:4]=[C:3]([OH:34])[CH:2]=1.[ClH:35]>C(O)(C)C>[CH:5]1[C:6]([C:7]2[S:15][C:14]3[CH:13]=[C:12]([OH:16])[CH:11]=[CH:10][C:9]=3[C:8]=2[C:17]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=2)=[O:18])=[CH:1][CH:2]=[C:3]([OH:34])[CH:4]=1.[ClH:35]

Participants

Conditions

Temperature: 27.5 °C

Procedure

To 400 ml of tetrahydrofuan, 100 g of raloxifene base was charged and 150 ml of hydrogen chloride gas in isopropyl alcohol was added at 5-10° C. (over a time period of about 1 hour). The reaction mass was stirred at 25-30° C. for 15 minutes, heated to 30-35° C. and maintained for 1 hour. The reaction mass was cooled to 0-5° C. and maintained for 30 minutes. The material was filtered, washed with chilled tetrahydrofuran followed by chilled methanol and vacuum dried for 30 minutes. The material was further dried under vacuum initially at 40-45° C. for about 2 hours and then at 50-55° C. for 8 hours.

Workup

temperatureheated to 30-35° C.
temperaturemaintained for 1 hour
temperatureThe reaction mass was cooled to 0-5° C.
temperaturemaintained for 30 minutes
filtrationThe material was filtered
washwashed with chilled tetrahydrofuran
temperatureby chilled methanol and vacuum
customdried for 30 minutes
customThe material was further dried under vacuum initially at 40-45° C. for about 2 hours
waitat 50-55° C. for 8 hours

Sources & evidence

ORD record: ord-7cf4d2e44b8146d28ba99ecbb027d6a5
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344149B2

Reaction notes

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