Trifluoroacetic acid → HCID 86757211, compound

HRID 1386971Notes

Reaction equation

HRID 1386971 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]1([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([C:23]3[C:24]4[CH:45]=[CH:44][CH:43]=[CH:42][C:25]=4[S:26][C:27]=3[C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][N:37]4[CH2:41][CH2:40][CH2:39][CH2:38]4)=[CH:30][CH:29]=3)=O)=[CH:17][CH:16]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1.C([SiH](CC)CC)C.[C:53]([OH:59])(C(F)(F)F)=[O:54].[C:60]([O-:63])([OH:62])=O.[Na+]>C1COCC1>[C:53]([OH:59])(=[O:54])[C:60]([OH:63])=[O:62].[C:53]([OH:59])(=[O:54])[C:60]([OH:63])=[O:62].[N:37]1([CH2:36][CH2:35][O:34][C:31]2[CH:30]=[CH:29][C:28]([C:27]3[S:26][C:25]4[CH:42]=[CH:43][CH:44]=[CH:45][C:24]=4[C:23]=3[CH2:21][C:18]3[CH:17]=[CH:16][C:15]([O:14][CH2:13][CH2:12][N:7]4[CH2:8][CH2:9][CH2:10][CH2:11]4)=[CH:20][CH:19]=3)=[CH:33][CH:32]=2)[CH2:38][CH2:39][CH2:40][CH2:41]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 10007482HCID 10007482, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 86757211HCID 86757211, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A slurry of 45 mg of LiAlH4 in 10 mL of THF was cooled to 0° C. and was treated with a solution of 200 mg (0.37 mmol) of 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 4-[2-(1-pyrrolidinyl)ethoxy]phenyl ketone (Part D) in 5 mL of THF. The reaction was stirred at 0° C. for 2 h and was quenched by the sequential addition of 1 mL of H2O, 1 mL of 2 N aq NaOH, and 1 mL of H2O. The two layers were separated and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were washed with 25 mL of brine, dried over K2CO3, and evaporated in vacuo. The residue was taken up in 10 mL of CH2Cl2, cooled to 0° C., and treated with 0.47 mL (2.94 mmol) of triethylsilane. After stirring at 0° C. for 6 h, the reaction was treated with 0.3 mL (3.9 mmol) of TFA, followed by an additional 16 h of stirring at 0° C. The reaction mixture was poured into 10 mL saturated aq NaHCO3 and the two layers were separated. The aqueous layer was extracted with CH2Cl2 (2×10 mL). The combined organic layers were dried over K2CO3 and evaporated in vacuo to give 233 mg of an oil which was purified by radial chromatography (SiO2; gradient 2-10% MeOH in CH2Cl2) to afford 158 mg (0.30 mmol; 81%) of the title compound as the free base. Conversion to the dioxalate salt was effected by the procedure detailed in Example 1, Part C.

Workup

  1. customwas quenched by the sequential addition of 1 mL of H2O, 1 mL of 2 N aq NaOH, and 1 mL of H2O
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (3×10 mL)
  4. washThe combined organic layers were washed with 25 mL of brine
  5. dry with materialdried over K2CO3
  6. customevaporated in vacuo
  7. temperaturecooled to 0° C.
  8. stirringAfter stirring at 0° C. for 6 h
  9. waitfollowed by an additional 16 h
  10. stirringof stirring at 0° C
  11. customthe two layers were separated
  12. extractionThe aqueous layer was extracted with CH2Cl2 (2×10 mL)
  13. dry with materialThe combined organic layers were dried over K2CO3
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-6c6119ef5d2f411e965f6a3b9d85b18a
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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