Trifluoroacetic acid → 2-(4-Aminophenyl)-6-benzyloxy-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]benzo[b]thiophene

HRID 650028Notes

Reaction equation

HRID 650028 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:40]=[CH:39][C:38]([O:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[CH:37][C:19]=3[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([N:28]([Si](C)(C)C)[Si](C)(C)C)=[CH:24][CH:23]=2)=O)[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C1COCC1.ClCCl>[CH2:42]([O:41][C:38]1[CH:39]=[CH:40][C:18]2[C:17]([CH2:15][C:5]3[CH:6]=[CH:7][C:8]([CH2:9][N:10]4[CH2:14][CH2:13][CH2:12][CH2:11]4)=[C:3]([O:2][CH3:1])[CH:4]=3)=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=3)[S:20][C:19]=2[CH:37]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 21226445Aluminium lithium hydrideHCID 224627436-Benzyloxy-2-[4-[bis(trimethylsilyl)amino]phenyl]-benzo[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]-phenyl ketone

Product 1

HCID 155495242-(4-Aminophenyl)-6-benzyloxy-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]benzo[b]thiopheneYield 94.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

6-Benzyloxy-2-[4-[bis(trimethylsilyl)amino]phenyl]-benzo[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]-phenyl ketone (0.73 g) was dissolved in THF (10 mL), cooled to 0° C. in an ice bath before treated with lithium aluminum hydride (110 mg) at 0° C. for 1 h, then quenched with water (1 mL) and sodium hydroxide (1.0 M, 1 mL). Stirring continued for 30 min. The reaction mixture was diluted with brine(30 mL) and extracted with dichloromethane (20 mL×3). The combined organic layers were dried with sodium sulfate and concentrated in vacuo to give the crude alcohol. This material was dissolved in dichloromethane (15 mL), treated with triethylsilane (1.5 mL) and trifluroacetic acid (1.5 mL) sequentially, allowed to stir at ambient temperature for 1.5 h, and concentrated under reduced pressure. The residue was extracted with dichloromethane (20 mL×3) from saturated aqueous sodium bicarbonate (30 mL). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with Et3N:MeOH:EtOAc (5:5:90) afforded the title compound as a yellow foam (0.53 g).

Workup

  1. customquenched with water (1 mL) and sodium hydroxide (1.0 M, 1 mL)
  2. additionThe reaction mixture was diluted with brine(30 mL)
  3. extractionextracted with dichloromethane (20 mL×3)
  4. dry with materialThe combined organic layers were dried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give the crude alcohol
  7. stirringto stir at ambient temperature for 1.5 h
  8. concentrationconcentrated under reduced pressure
  9. extractionThe residue was extracted with dichloromethane (20 mL×3) from saturated aqueous sodium bicarbonate (30 mL)
  10. dry with materialThe combined organic layers were dried with sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-cd2fcdbead1f4d33b6536f6dfb5193fc
Source dataset
uspto-grants-2001_08
Patent number
US06271227B1

Reaction notes

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