Methanol → Raloxifene

HRID 850723Notes

Reaction equation

HRID 850723 reaction equation
B(Cl)(Cl)Cl.C[O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)=[CH:19][CH:18]=3)=[O:16])=[C:13]([C:32]3[CH:37]=[CH:36][C:35]([O:38]C)=[CH:34][CH:33]=3)[S:12][C:11]=2[CH:40]=1.CO>ClCCCl>[OH:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15](=[O:16])[C:17]3[CH:18]=[CH:19][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]4)=[CH:21][CH:22]=3)=[C:13]([C:32]3[CH:33]=[CH:34][C:35]([OH:38])=[CH:36][CH:37]=3)[S:12][C:11]=2[CH:40]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 25135Boron TrichlorideHCID 10767755Raloxifene Bismethyl Ether

Product 1

HCID 5035RaloxifeneYield 85.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
35 °C

Procedure

Boron trichloride gas is condensed into a cold graduated cylinder (2.8 ml), and added to a solution of [6-methoxy-2-(4-methoxyphenyl)-benzo-[b]-thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]phenyl] methanone (6.37 g, 12.7 mmol) in 52 ml of 1,2-dichloroethane. The resulting solution is heated to 35° C. After about 16 hours the reaction is complete. Methanol (30 ml) is added to the reaction mixture over a 20 minute period, causing the methanol to reflux. The resulting slurry was stirred at 25° C. After 1 hour, the crystalline product is filtered, washed with cold methanol (8 ml), and dried at 40 ° C. in vacuo to give 5.14 g of the title compound. mp 225° C.

Workup

  1. customcondensed into a cold graduated cylinder (2.8 ml)
  2. temperatureto reflux
  3. waitAfter 1 hour
  4. filtrationthe crystalline product is filtered
  5. washwashed with cold methanol (8 ml)
  6. customdried at 40 ° C. in vacuo

Sources & evidence

ORD record
ord-e03546e5bc984fb4b41f570ff213e2a4
Source dataset
uspto-grants-2000_01
Patent number
US06018056

Reaction notes

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