6-Methoxy-2-(4-Methoxyphenyl)benzo[b]thiophene-3-Carboxylic Acid Chloride → Raloxifene Bismethyl Ether

HRID 850728Notes

Reaction equation

HRID 850728 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11](Cl)=[O:12])=[C:9]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[S:8][C:7]=2[CH:22]=1.[N:23]1([CH2:29][CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([Mg]Br)=[CH:34][CH:33]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:35]3[CH:34]=[CH:33][C:32]([O:31][CH2:30][CH2:29][N:23]4[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)=[CH:37][CH:36]=3)=[O:12])=[C:9]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[S:8][C:7]=2[CH:22]=1

Participants

4

Reactant 2

HCID 109805146-Methoxy-2-(4-Methoxyphenyl)benzo[b]thiophene-3-Carboxylic Acid ChlorideHCID 178419641HCID 178419641, compound

Product 1

HCID 10767755Raloxifene Bismethyl Ether

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene-3-carboxylic acid chloride (98.5 mg, 0.296 mmol) in tetrahydrofuran (3 ml) at 2° C. under nitrogen is added dropwise via syringe a solution of 4-[2-(1-piperidinyl)ethoxy]phenylmagnesium bromide (0.48 ml of 0.75 M solution, 0.36 mmol). The resulting mixture is stirred at that temperature for 16 hours, then quenched by addition of methyl alcohol. It is then partitioned between methylene chloride and saturated aqueous ammonium chloride, and the separated organic layer is dried over magnesium sulfate, filtered and concentrated to an oil, which is chromatographed on silica gel (10:5:1 hexanes:dichloromethane:triethylamine) to afford a product-containing fraction, which is further chromatographed on silica gel (10:1:1 hexanes:dichloromethane:triethylamine) to afford title compound as an oil: 88.4 mg (60%). 1H NMR spectrum identical to authentic sample. Anal. Calcd. for C30H31NO4S: C, 71.83; H, 6.23; N, 2.79; S, 6.39. Found: C, 71.59; H, 6.32; N, 2.69; S, 6.14.

Workup

  1. customquenched by addition of methyl alcohol
  2. customIt is then partitioned between methylene chloride and saturated aqueous ammonium chloride
  3. dry with materialthe separated organic layer is dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to an oil, which
  6. customis chromatographed on silica gel (10:5:1 hexanes:dichloromethane:triethylamine)
  7. customto afford a product-containing fraction, which
  8. customis further chromatographed on silica gel (10:1:1 hexanes:dichloromethane:triethylamine)

Sources & evidence

ORD record
ord-5b949738d4184dc1a290de3ca65f9cf7
Source dataset
uspto-grants-2000_01
Patent number
US06018056

Reaction notes

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