1-methyl-5-(tributylstannyl)-1H-1,2,3-triazole → HCID 67717683, compound

HRID 355372Notes

Reaction equation

HRID 355372 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18](Br)[CH:17]=2)[C@@H:9]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:33][N:34]1[C:38]([Sn](CCCC)(CCCC)CCCC)=[CH:37][N:36]=[N:35]1>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:38]3[N:34]([CH3:33])[N:35]=[N:36][CH:37]=3)[CH:17]=2)[C@@H:9]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 226098261-methyl-5-(tributylstannyl)-1H-1,2,3-triazoleHCID 67717494HCID 67717494, compound

Product 1

HCID 67717683HCID 67717683, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Procedure

Bis(triphenylphosphine)palladium dichloride (5.0 mg) was added to a degassed solution of [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[3-bromo-5-(trifluoromethyl)phenylmethoxy]piperidine (330 mg), and 1-methyl-5-tributylstannanyl-1H-[1,2,3]triazole (713 mg) in dry toluene (15.0 ml) under a dry nitrogen atmosphere. The resulting solution was warmed to reflux for 4 hours. After this time the reaction was cooled to room temperature and the solvent removed under reduced pressure. The residue was partitioned between aqueous NaHCO3 solution (10 ml, satd.) and ethyl acetate. The organic layer was washed with brine (10 ml), dried over MgSO4, filtered and the solvent removed under pressure. Purification by MPLC (1:1 ethyl acetate/n-hexane) afforded [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[3-(1-methyl-1H-[1,2,3]triazol-5-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine as a yellow foam (330 mg). 1H NMR (360 MHz,CDCl3) δ 1.45 (9H, s), 1.74 (2H, m), 2.00 (2H, m), 2.75 (1H, t d, J=7.2, 3.0 Hz), 3.91 (2H,m), 4.03 (3H, s), 4.74 (2H, s), 5.71 (1H, br s), 7.27-7.33 (3H, m), 7.44-7.62 (5H, m), 7.75 (1H, s).

Workup

  1. temperatureThe resulting solution was warmed
  2. temperatureto reflux for 4 hours
  3. customthe solvent removed under reduced pressure
  4. customThe residue was partitioned between aqueous NaHCO3 solution (10 ml, satd.) and ethyl acetate
  5. washThe organic layer was washed with brine (10 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed under pressure
  9. customPurification by MPLC (1:1 ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-f097cad735fc49848cafc8142904ec5d
Source dataset
uspto-grants-1998_11
Patent number
US05830892

Reaction notes

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