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

HRID 1387103Notes

Reaction equation

HRID 1387103 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=3[C:24]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH:33]4[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34]4)=[CH:28][CH:27]=3)=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C1COCC1.ClCCl>[CH2:38]([N:35]1[CH2:36][CH2:37][CH:33]([O:32][C:29]2[CH:30]=[CH:31][C:26]([CH2:24][C:16]3[C:17]4[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=4[S:19][C:15]=3[C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)=[CH:10][CH:11]=3)=[CH:27][CH:28]=2)[CH2:34]1)[CH3:39]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 211828674-[(1-Ethylpyrrolidin-3-yl)oxy]phenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl KetoneHCID 21226445Aluminium lithium hydride

Product 1

HCID 206667944-[(1-Ethylpyrrolidin-3-yl)oxy]benzyl-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]-thiopheneYield 82.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

The ketone of Example 170 (112 mg, 0.20 mmol) in THF (3 mL) was treated with lithium aluminum hydride (25 mg) at 0° C. for 1 h, then quenched with water (1 mL) and sodium hydroxide (5.0 M, 1 mL). Stirring continued for 20 min. The reaction mixture was diluted with brine (50 mL) and extracted with dichloromethane (3×50 mL). The combined organic layers were dried with sodium sulfate and concentrated in vacuo to give a white foam-like material. This material was dissolved in dichloromethane (5 mL), treated with triethylsilane (0.25 mL) and trifluroacetic acid (0.20 mL) at 0° C. for 1 h, and then concentrated under reduced pressure. The residue was extracted with dichloromethane (50 mL×3) which was washed with saturated aqueous sodium bicarbonate (50 mL). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with Et3N:MeOH:EtOAc (5:5:90) afforded the product as a colorless oil (87 mg, 78%).

Workup

  1. customquenched with water (1 mL) and sodium hydroxide (5.0 M, 1 mL)
  2. additionThe reaction mixture was diluted with brine (50 mL)
  3. extractionextracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic layers were dried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a white foam-like material
  7. concentrationconcentrated under reduced pressure
  8. extractionThe residue was extracted with dichloromethane (50 mL×3) which
  9. washwas washed with saturated aqueous sodium bicarbonate (50 mL)
  10. dry with materialThe combined organic layers were dried with sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-9b9fd0ff1e6245c487598ad20dd7fe5d
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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