Trifluoroacetic acid → 6-Hydroxy-2-[4-(2-methoxy-2-oxoethoxy)phenyl]-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]benzo[b]thiophene

HRID 1595041Notes

Reaction equation

HRID 1595041 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:32]=[CH:31][C:30]([O:33]CC4C=CC=CC=4)=[CH:29][C:19]=3[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[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-].[CH2:47]([SiH](CC)CC)C.F[C:55](F)(F)[C:56]([OH:58])=[O:57]>C1COCC1.ClCCl>[OH:33][C:30]1[CH:31]=[CH:32][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:23]=[CH:24][C:25]([O:28][CH2:55][C:56]([O:58][CH3:47])=[O:57])=[CH:26][CH:27]=3)[S:20][C:19]=2[CH:29]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 21226445Aluminium lithium hydrideHCID 224627986-Benzyloxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl 3-methoxy-4-(1-pyrrolidinylmethyl)phenyl ketone

Product 1

HCID 217063346-Hydroxy-2-[4-(2-methoxy-2-oxoethoxy)phenyl]-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]benzo[b]thiopheneYield 78%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-Benzyloxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl 3-methoxy-4-(1-pyrrolidinylmethyl)phenyl ketone (2.75 g, 5.0 mmol) in THF (25 mL) was treated with lithium aluminum hydride (420 mg) at 0° C. for 2 h, then quenched with water (1 mL) and sodium hydroxide (1.0 M, 3 mL). Stirring was continued for 45 min. The reaction mixture was diluted with brine (100 mL) and extracted with dichloromethane (100 mL×3). 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 (50 mL), treated with triethylsilane (6.0 mL) and trifluroacetic acid (5.0 mL) at 0° C. for 2 h, and concentrated under reduced pressure. The residue was extracted with dichloromethane (100 mL×3) which was washed with saturated aqueous sodium bicarbonate (100 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 white solid (2.1 g, 78%).

Workup

  1. customquenched with water (1 mL) and sodium hydroxide (1.0 M, 3 mL)
  2. additionThe reaction mixture was diluted with brine (100 mL)
  3. extractionextracted with dichloromethane (100 mL×3)
  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 (100 mL×3) which
  9. washwas washed with saturated aqueous sodium bicarbonate (100 mL)
  10. dry with materialThe combined organic layers were dried with sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e8b3e64260a54f1f8f2618109df0310a
Source dataset
uspto-grants-2001_09
Patent number
US06284756B1

Reaction notes

Loading…