Hydrochloric Acid → 1-{5-[5-(4-Chlorophenyl)pyridin-2-ylethynyl]-2-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl}-2,2,2-trifluoroethanol

HRID 734867Notes

Reaction equation

HRID 734867 reaction equation
C[Si](C)(C)[C:3]([F:6])([F:5])[F:4].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[CH:18][C:19]([C:22]#[C:23][C:24]3[CH:25]=[CH:26][C:27]([O:32][CH2:33][CH2:34][N:35]4[CH2:40][CH2:39][CH:38]([CH3:41])[CH2:37][CH2:36]4)=[C:28]([CH:31]=3)[CH:29]=[O:30])=[N:20][CH:21]=2)=[CH:12][CH:11]=1.[F-].[Cs+].Cl.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:17]=[CH:18][C:19]([C:22]#[C:23][C:24]3[CH:25]=[CH:26][C:27]([O:32][CH2:33][CH2:34][N:35]4[CH2:36][CH2:37][CH:38]([CH3:41])[CH2:39][CH2:40]4)=[C:28]([CH:29]([OH:30])[C:3]([F:6])([F:5])[F:4])[CH:31]=3)=[N:20][CH:21]=2)=[CH:14][CH:15]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 86601135HCID 86601135, compound

Product 1

HCID 578452971-{5-[5-(4-Chlorophenyl)pyridin-2-ylethynyl]-2-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl}-2,2,2-trifluoroethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

0.523 mL (1.05 mmol) of trimethyltrifluoromethylsilane (2M in THF) was slowly added dropwise at −10° C. to a solution of 0.39 g (0.85 mmol) of 5-[5-(4-chlorophenyl)pyridin-2-ylethynyl]-2-[2-(4-methylpiperidin-1-yl)ethoxy]benzaldehyde (Example 14.1c) and 13 mg (0.087 mmol) of cesium fluoride in 10 mL of THF and the reaction mixture was stirred for 2 hours at −10° C. 7 mL of 1M aqueous HCl were added and the mixture was stirred. The reaction mixture was made alkaline by the addition of saturated aqueous potassium carbonate solution and the phases were separated. The aqueous phase was extracted with EtOAc, and the combined organic extracts were dried over magnesium sulfate and evaporated down in vacuo. The crude product was purified by chromatography (silica gel, EtOAc/MeOH/sat. aqueous ammonia 95:5:0.5). Yield: 25 mg (5% of theoretical); C29H28ClF3N2O2 (M=528.993); calc.: (M+H)+:529/531 (Cl); found: molpeak (M+H)+:529/531 (Cl); HPLC-MS: 5.95 minutes (method B).

Workup

  1. stirringthe mixture was stirred
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with EtOAc
  4. dry with materialthe combined organic extracts were dried over magnesium sulfate
  5. customevaporated down in vacuo
  6. customThe crude product was purified by chromatography (silica gel, EtOAc/MeOH/sat. aqueous ammonia 95:5:0.5)
  7. custom5.95 minutes (method B)

Sources & evidence

ORD record
ord-50c61e167aea4572b5857c96c54f5b69
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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