Sodium Bicarbonate → tert-butyl (3S)-3-({4-[4-(1-benzofuran-5-yl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)pyrrolidine-1-carboxylate

HRID 525166Notes

Reaction equation

HRID 525166 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][N:10]=[C:9]2[CH2:14][C@@H:15]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]3[O:42][CH:41]=[CH:40][C:39]=3[CH:43]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.C(OCC)(=O)C>[O:42]1[C:38]2[CH:37]=[CH:36][C:35]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12](=[O:13])[NH:11][N:10]=[C:9]4[CH2:14][C@@H:15]4[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]4)=[CH:4][CH:3]=3)=[CH:43][C:39]=2[CH:40]=[CH:41]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 27951905-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuranHCID 673758331,1-dimethylethyl (3S)-3-{[4-(4-bromophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-1-pyrrolidinecarboxylate

Product 1

HCID 67376548tert-butyl (3S)-3-({4-[4-(1-benzofuran-5-yl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)pyrrolidine-1-carboxylateYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a sealed pressure tube, a mixture of 1,1-dimethylethyl (3S)-3-{[4-(4-bromophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-1-pyrrolidinecarboxylate (2.5 g, 5.91 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (1.514 g, 6.20 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.241 g, 0.295 mmol), and sodium bicarbonate (1.488 g, 17.72 mmol) in 1,4-dioxane (30 mL) and water (15 mL) was stirred at 100° C. for 24 h. The reaction was cooled to room temperature. The reaction was diluted with ethyl acetate (300 mL) and water (100 mL), and the layers were separated. The aqueous layer was acidified to pH˜6 using a 1N aq HCl solution and then extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by silica gel chromatography (Analogix IF280, SF40-115g, Solvent A: ethyl acetate; Solvent B: 10% methanol/dichloromethane; Gradient: 100% A for 10 min, then 0-50% B/A over 20 min) provided the title compound as a tan solid (2.6 g, 96%). MS(ES)+ m/e 461.4 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customthe layers were separated
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by silica gel chromatography (Analogix IF280, SF40-115g, Solvent A
  7. waitGradient: 100% A for 10 min

Sources & evidence

ORD record
ord-805c79092eb846d08cc86873d82ed16c
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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