Trifluoroacetic acid → 3-[4-[2-(2-Oxopyrrolidin-1-yl)ethoxy]benzyl]-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene

HRID 1700774Notes

Reaction equation

HRID 1700774 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([C:18]2[C:19]3[CH:40]=[CH:39][CH:38]=[CH:37][C:20]=3[S:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:25][CH:24]=2)=O)=[CH:12][CH:11]=1.[BH4-].[Li+].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C1COCC1.CO.[Cl-].[Na+].O.ClCCl>[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:18]2[C:19]3[CH:40]=[CH:39][CH:38]=[CH:37][C:20]=3[S:21][C:22]=2[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:25][CH:24]=2)=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 4148881Lithium borohydrideHCID 183185242-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]-benzo[b]thiophen-3-yl 4-[2-(2-Oxopyrrolidin-1-yl)ethoxy]-phenyl Ketone

Product 1

HCID 183185073-[4-[2-(2-Oxopyrrolidin-1-yl)ethoxy]benzyl]-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiopheneYield 23.1%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 4-[2-(2-oxopyrrolidin-1-yl)ethoxy]phenyl ketone (120 mg) was dissolved in THF/MeOH (3.0/0.3 mL) and treated with lithium borohydride (40 mg) in one portion and allowed to stir at ambient temperature for 4 h. 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 (3.0 mL), treated with triethylsilane (0.25 mL) and trifluroacetic acid (0.2 mL) sequentially, allowed to stir at ambient temperature for 2 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 (27 mg).

Workup

  1. extractionextracted with dichloromethane (20 mL×3)
  2. dry with materialThe combined organic layers were dried with sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give the crude alcohol
  5. stirringto stir at ambient temperature for 2 h
  6. concentrationconcentrated under reduced pressure
  7. extractionThe residue was extracted with -dichloromethane (20 mL×3) from saturated aqueous sodium bicarbonate (30 mL)
  8. dry with materialThe combined organic layers were dried with sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3c54582c75cb4ec991260284e880c354
Source dataset
uspto-grants-2002_02
Patent number
US06350774B1

Reaction notes

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