Methanol → 6-Methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-Methoxy-4-(1-pyrrolidinylmethyl)phenyl Ketone

HRID 1387112Notes

Reaction equation

HRID 1387112 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][C:19]=3[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:24][CH:23]=2)=[O:16])[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.[CH:41](N(C(C)C)CC)(C)C.C[Si](C=[N+]=[N-])(C)C.CO>CO.CC#N>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:19]=3[S:20][C:21]=2[C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:26][CH:27]=2)=[O:16])[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 167693Trimethylsilyldiazomethane3×HCID 10650441HCID 10650441, compound

Product 1

HCID 211826496-Methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-Methoxy-4-(1-pyrrolidinylmethyl)phenyl KetoneYield 43.6%

Reagents, catalysts & solvents 1

HCID 21959252Acetonitrile methanolSolvent

Procedure

To a mixture of (210 mg, 0.37 mmol) of 6-hydroxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-methoxy-4-(1-pyrrolidinylmethyl)phenyl ketone (Example 163, Part C) in 2.0 mL of MeOH/CH3CN solution (1:9 ratio) was added (0.091 mL, 0.52 mmol) of diisopropylethylamine and (0.26 mL, 0.52 mmol) 2 M (trimethylsilyl)diazomethane in hexanes at room temperature. The reaction was stirred for 24 h. Another portion (0.20 mL, 0.40 mmol) of 2 M (trimethylsilyl)diazomethane in hexanes was added along with 0.5 mL of MeOH, and the solution was stirred at room temperature for 24 h. Another portion (0.10 mL, 0.20 mmol) of 2 M (trimethylsilyl)diazomethane in hexanes was added, and the solution was stirred at room temperature for 24 h. The reaction mixture was concentrated to dryness under reduced pressure and then taken up in 30 mL of H2O and washed with 25 mL of H2O and 1:1 satd. NaHCO3-brine solution which were back extracted with CH2Cl2 (3×30 mL) and EtOAc (1×30 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. Purification by flash chromatography (silica gel, 7% [10% conc NH4OH in MeOH]/CH2Cl2) afforded 92 mg (43%) of a yellow foam.

Workup

  1. stirringthe solution was stirred at room temperature for 24 h
  2. stirringthe solution was stirred at room temperature for 24 h
  3. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  4. washwashed with 25 mL of H2O and 1:1 satd
  5. extractionNaHCO3-brine solution which were back extracted with CH2Cl2 (3×30 mL) and EtOAc (1×30 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (silica gel, 7% [10% conc NH4OH in MeOH]/CH2Cl2)

Sources & evidence

ORD record
ord-b08a472c539e49baa64bf29ab21c03c6
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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