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

HRID 650025Notes

Reaction equation

HRID 650025 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:17]3[C:18]4[CH:34]=[CH:33][CH:32]=[CH:31][C:19]=4[S:20][C:21]=3[C:22]3[CH:27]=[CH:26][C:25]([CH2:28][C:29]#[N:30])=[CH:24][CH:23]=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>[C:29]([CH2:28][C:25]1[CH:24]=[CH:23][C:22]([C:21]2[S:20][C:19]3[CH:31]=[CH:32][CH:33]=[CH:34][C:18]=3[C:17]=2[CH2:15][C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:14][CH:13]=2)=[CH:27][CH:26]=1)#[N:30]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 21226445Aluminium lithium hydrideHCID 224627222-[4-(Cyanomethyl)phenyl]benzo[b]thiophen-3-yl 4-[2-(1-pyrrolidinyl)ethoxy]phenyl ketone

Product 1

HCID 224627452-[4-(Cyanomethyl)phenyl]-3-[4-[2-(1-pyrrolidinyl)ethoxy]benzyl]benzo[b]thiopheneYield 69.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-[4-(Cyanomethyl)phenyl]benzo[b]thiophen-3-yl 4-[2-(1-pyrrolidinyl)ethoxy]phenyl ketone (158 mg) in THF (5.0 mL) was treated with lithium aluminum hydride (13 mg) at 0° C. for 2 h, and then quenched with water (0.5 mL) and sodium hydroxide (5.0 M, 0.5 mL). Stirring was continued for 10 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 yellow foam-like material. This material was dissolved in dichloromethane (5 mL), treated with triethylsilane (0.3 mL) and trifluroacetic acid (0.2 mL) at 0° C. for 1.5 h, and concentrated under reduced pressure. The residue was extracted with dichloromethane (50 mL×3) from saturated aqueous sodium bicarbonate (50 mL). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with Et3N:EtOAc (0-5%) afforded the product (106 mg).

Workup

  1. customquenched with water (0.5 mL) and sodium hydroxide (5.0 M, 0.5 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 yellow foam-like material
  7. concentrationconcentrated under reduced pressure
  8. extractionThe residue was extracted with dichloromethane (50 mL×3) from saturated aqueous sodium bicarbonate (50 mL)
  9. dry with materialThe combined organic layers were dried with sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-7788e61d3c6449a3a2dc649083d4d563
Source dataset
uspto-grants-2001_08
Patent number
US06271227B1

Reaction notes

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