Trifluoroacetic acid → HCID 10531733, compound

HRID 1387072Notes

Reaction equation

HRID 1387072 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][N:20]4[CH2:24][CH2:23][CH2:22][CH2:21]4)=[C:15]([Br:25])[CH:14]=3)=O)=[C:9]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][N:35]4[CH2:39][CH2:38][CH2:37][CH2:36]4)=[CH:28][CH:27]=3)[S:8][C:7]=2[CH:40]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C1COCC1.O.[OH-].[Na+]>[Br:25][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[CH2:19][N:20]1[CH2:21][CH2:22][CH2:23][CH2:24]1)[CH2:11][C:10]1[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:40][C:7]=2[S:8][C:9]=1[C:26]1[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][N:35]2[CH2:36][CH2:37][CH2:38][CH2:39]2)=[CH:30][CH:31]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 12052TriethylsilaneHCID 10746430HCID 10746430, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 10531733HCID 10531733, compoundYield 72.2%

Reagents, catalysts & solvents 3

HCID 962WaterCatalyst2×HCID 14798Sodium HydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 4-[3-bromo-4-[(1-pyrrolidinyl)methyl]phenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone (Example 137; part C) (0.2 g; 0.32 mmol) in 3.0 mL of THF was added 18.4 mg (0.48 mmol) of LAH at 0° C. The bath was removed and the mixture was stirred for 1 h. Hydrolysis was effected by addition of 1 drop of water, 1 drop of 5N NaOH, and 3 drops of water, followed by stirring for 1 h. The mixture was filtered, the filtrate was concentrated and, the intermediate carbinol was dried in vacuo for 25 min. The carbinol was dissolved in methylene chloride (3.0 mL) under argon atmosphere and cooled in an ice-water bath. Triethylsilane (0.36 mL; 2.26 mmol) was added, followed by dropwise addition of 0.25 mL (3.23 mmol) of TFA. Upon completion of addition of TFA, the bath was removed and stirring was continued for 2 h. Saturated aqueous sodium bicarbonate (25 mL) was added, and extraction was carried out with EtOAc. The combined organics were washed with brine and dried by passage through sodium sulfate. The title compound (0.14 g; 72% yield) was isolated as a colorless oil by flash chromatography on silica gel eluting with a gradient of EtOAc(100-95%)/Et3N(0-5%).

Workup

  1. customThe bath was removed
  2. customHydrolysis
  3. stirringby stirring for 1 h
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. dry with materialthe intermediate carbinol was dried in vacuo for 25 min
  7. dissolutionThe carbinol was dissolved in methylene chloride (3.0 mL) under argon atmosphere
  8. temperaturecooled in an ice-water bath
  9. customthe bath was removed
  10. stirringstirring
  11. waitwas continued for 2 h
  12. additionSaturated aqueous sodium bicarbonate (25 mL) was added
  13. extractionextraction
  14. washThe combined organics were washed with brine
  15. dry with materialdried by passage through sodium sulfate

Sources & evidence

ORD record
ord-b3cbf2aecc9a46048ce2a2d5008ae090
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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