Trifluoroacetic acid → 6-Hydroxy-3-(3-methoxy-4-((1-pyrrolidinyl)methyl)benzyl)-2-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl)benzo(b)thiophene

HRID 377408Notes

Reaction equation

HRID 377408 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][C:19]=3[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[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>[OH:40][C:37]1[CH:38]=[CH:39][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]([O:28][CH2:29][CH2:30][N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)=[CH:24][CH:23]=3)[S:20][C:19]=2[CH:36]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 10650441HCID 10650441, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 104824786-Hydroxy-3-(3-methoxy-4-((1-pyrrolidinyl)methyl)benzyl)-2-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl)benzo(b)thiopheneYield 76.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

6-Hydroxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo-[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]phenyl ketone (368006, 1.17 g, 2.10 mmol) in dry THF (40 mL) at 0° C. under argon was treated with lithium aluminum hydride (164 mg) for 1 h, then quenched with water(1 mL) and sodium hydroxide (1.0M, 3 mL). Stirring continued for 30 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 (30 mL), treated with triethylsilane (3.0 mL), cooled to 0° C. under argon, and followed by slow addition of trifluroacetic acid (2.5 mL). The resulting mixture was stirred at 0° C. for 2 h and then concentrated under reduced pressure. The residue was extracted with dichloromethane (50 mL×3) which extracts were washed with saturated aqueous sodium bicarbonate (100 mL). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with Et3N:MeOH:EtOAc (5:10:85) afforded the product as a white solid (0.87 g, 76%).

Workup

  1. customquenched with water(1 mL) and sodium hydroxide (1.0M, 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. stirringThe resulting mixture was stirred at 0° C. for 2 h
  8. concentrationconcentrated under reduced pressure
  9. extractionThe residue was extracted with dichloromethane (50 mL×3) which extracts
  10. washwere washed with saturated aqueous sodium bicarbonate (100 mL)
  11. dry with materialThe combined organic layers were dried with sodium sulfate
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-721c0af1f5b840a1811ea380ca417220
Source dataset
uspto-grants-2000_02
Patent number
US06025382

Reaction notes

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