Trifluoroacetic acid → HCID 86757213, compound

HRID 1387063Notes

Reaction equation

HRID 1387063 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=3[C:24]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][NH:35][CH2:36][CH3:37])=[CH:28][CH:27]=3)=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C[AlH]CC(C)C)C.[SiH](CC)(CC)CC.[C:54]([OH:60])(C(F)(F)F)=[O:55].[C:61]([O-:64])([OH:63])=O.[Na+]>C1COCC1>[C:54]([OH:60])(=[O:55])[C:61]([OH:64])=[O:63].[C:54]([OH:60])(=[O:55])[C:61]([OH:64])=[O:63].[CH2:36]([NH:35][CH2:34][CH2:33][O:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:24][C:16]2[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[S:19][C:15]=2[C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:10][CH:11]=2)=[CH:27][CH:28]=1)[CH3:37]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 14487Diisobutylaluminum hydrideHCID 516892Sodium BicarbonateHCID 10815686HCID 10815686, compound

Product 1

HCID 86757213HCID 86757213, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 0° C. solution of 4-[2-(ethylamino)ethoxy]phenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone (390 mg, 0.758 mmol; Part B) in 5 mL of anhydrous THF was treated with DIBAL-H (1.5 mL, 1.52 mmol, 1M solution in toluene) dropwise via a syringe. After 1 h at 0° C., the excess DIBAL-H was quenched with excess MeOH (approximately 1 mL), 5 mL of saturated Na+K+ tartrate and 5 mL of EtOAc were added, and the biphasic mixture was vigorously stirred for 1.5 h at ambient temperature. The layers were separated, and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was dissolved in 5 mL of 1,2-dichloroethane and Et3SiH (848 μL, 5.31 mmol). Upon cooling to 0° C., TFA (584 μL, 7.58 mmol) was added in a dropwise fashion. After 1.5 h, the reaction mixture was poured into 50 mL of saturated aqueous NaHCO3 solution. The aqueous phase was extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification by radial chromatography (SiO2; gradient of 90:8:2 to 85:10:5 hexanes-THF-TEA) afforded 175 mg (0.35 mmol; 42%) of a yellow oil. The free base was converted to the title dioxalate salt according to the conditions described in Example 1, Part C.

Workup

  1. customthe excess DIBAL-H was quenched with excess MeOH (approximately 1 mL), 5 mL of saturated Na+K+ tartrate and 5 mL of EtOAc
  2. additionwere added
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude residue was dissolved in 5 mL of 1,2-dichloroethane
  9. temperatureUpon cooling to 0° C.
  10. waitAfter 1.5 h
  11. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  12. dry with materialThe combined organic layers were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customPurification by radial chromatography (SiO2; gradient of 90:8:2 to 85:10:5 hexanes-THF-TEA)
  16. customafforded 175 mg (0.35 mmol; 42%) of a yellow oil

Sources & evidence

ORD record
ord-fc7080315ddc46d28ed0854f72af4c37
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

Loading…