1-methyl-5-(tributylstannyl)-1H-1,2,3-triazole → [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-{[5-(1-methyl-1H-[1,2,3]triazol-5-yl)benzofuran-7-yl]methyloxy}piperidine

HRID 1602929Notes

Reaction equation

HRID 1602929 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[C:24]3[O:23][CH:22]=[CH:21][C:20]=3[CH:19]=[C:18](Br)[CH:17]=2)[C@@H:9]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:32][N:33]1[C:37]([Sn](CCCC)(CCCC)CCCC)=[CH:36][N:35]=[N:34]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[C:24]3[O:23][CH:22]=[CH:21][C:20]=3[CH:19]=[C:18]([C:37]3[N:33]([CH3:32])[N:34]=[N:35][CH:36]=3)[CH:17]=2)[C@@H:9]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 226098261-methyl-5-(tributylstannyl)-1H-1,2,3-triazoleHCID 57239557[2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[(5-bromobenzofuran-7-yl)methyloxy]piperidine

Product 1

HCID 18395014[2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-{[5-(1-methyl-1H-[1,2,3]triazol-5-yl)benzofuran-7-yl]methyloxy}piperidineYield 45.7%

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-[(5-bromobenzofuran-7-yl)methyloxy]piperidine (111 mg), and 1-methyl-5-tributylstannanyl-1H-[1,2,3]triazole (165 mg) in dry toluene (5.0 ml) under a dry nitrogen atmosphere. The resulting solution was warmed to reflux for 18 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, sat) 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-{[5-(1-methyl-1H-[1,2,3]triazol-5-yl)benzofuran-7-yl]methyloxy}piperidine as a yellow foam (51 mg). 1H NMR (360 MHz,CDCl3)δ1.45 (9H, s), 1.51-1.83 (5H, m), 2.73 (1H, t d, J=7.0, 3.0 Hz), 3.94 (1H, m), 3.96 (3H, s), 5.02 (2H, d, J=1.0 Hz), 5.76 (1H, br s), 6.84 (1H, d, J=1.0 Hz), 7.26 (4H, m), 7.55 (3H, m), 7.70 (2H, br s); MS m/z CI+ 489 (M+H+).

Workup

  1. temperatureThe resulting solution was warmed
  2. temperatureto reflux for 18 hours
  3. customthe solvent removed under reduced pressure
  4. customThe residue was partitioned between aqueous NaHCO3 solution (10 ml, sat) 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-09dfed888c694ed1abee2ce90b774948
Source dataset
uspto-grants-1999_11
Patent number
US05985896

Reaction notes

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