Tetrahydrofuran → 4-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridine

HRID 2401736Notes

Reaction equation

HRID 2401736 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=1.[Cl-].[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][Zn+])=[CH:30][CH:29]=1.O1CCCC1>CCOC(C)=O.[Cl-].[NH4+].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][C:2]2[CH:3]=[C:4]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[S:5][C:6]=2[C:7]2[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=2)=[CH:30][CH:29]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 667492834-[4-Bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridineHCID 178478120HCID 178478120, compound

Product 1

HCID 680066934-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridineYield 76%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Bis(tri-t-butylphosphine)palladium(0) (4.38 mg, 0.00857 mmol) and 4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridine (0.075 g, 0.17 mmol) were combined in a dry round bottomed flask fitted with a stirbar and sealed with a septum. The flask was evacuated/refilled with nitrogen three times then a solution of 4-chlorobenzylzinc chloride in tetrahydrofuran (0.50M, 0.720 mL, 0.360 mmol) was added dropwise via a syringe. A nitrogen line was attached and the reaction was stirred at rt for 30 minutes, then at 60° C. for ˜2 hours. The reaction was cooled to rt, diluted with EtOAc and saturated ammonium chloride solution, then the mixture was transferred to a separatory funnel. The organic layer was separated and the aqueous layer was extracted twice more with EtOAc. The organics were combined, washed with bicarbonate solution, then brine, then dried over sodium sulfate. The mixture was filtered then evaporated in vacuo and the residue was purified by column chromatography on silica, elution 100% hexane to 100% EtOAc to afford the title compound as a light yellow oil. Yield 63 mg (76% yield). LCMS: (FA) ES+, 483, 485.

Workup

  1. customfitted with a stirbar
  2. customsealed with a septum
  3. additionThe flask was evacuated/refilled with nitrogen three times
  4. waitat 60° C. for ˜2 hours
  5. temperatureThe reaction was cooled to rt
  6. customthe mixture was transferred to a separatory funnel
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted twice more with EtOAc
  9. washwashed with bicarbonate solution
  10. dry with materialbrine, then dried over sodium sulfate
  11. filtrationThe mixture was filtered
  12. customthen evaporated in vacuo
  13. customthe residue was purified by column chromatography on silica, elution 100% hexane to 100% EtOAc

Sources & evidence

ORD record
ord-22b2ed50f7e44374a8cc2ac006dda34b
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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