Reaktion #612312

Reaktionsgleichung

4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran

potassium carbonate

→

title product

Ausbeute 69.0%

4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Ausbeute 69.0%

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was cooled to room temperature
2. 2
   SonstigeThe layers were separated
3. 3
   Extraktionwas extracted with ethyl acetate (2×50 mL)
4. 4
   TrocknenThe combined organic layers were dried over MgSO4
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigePurification of the residue by silica gel chromatography (Analogix IF280, 0-10% MeOH/CH2Cl2, SF15-12 g, 20 min)
7. 7
   Sonstigefollowed by another purification (100% EtOAc for 10 min
8. 8
   Sonstige0-8% MeOH/CH2Cl2 for 15 min) and finally subsequent purification by silica gel chromatography (Analogix IF280, SF15-4 g, Solvent A=EtOAc
9. 9
   workup.WAITGradient: 100% A for 10 min then ramped to 100% B over 20 min

Vorschrift

In a microwave vial, a mixture of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (322 mg, 0.77 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (208 mg, 0.85 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (32 mg, 0.04 mmol) in 2M aq potassium carbonate solution (1.5 mL, 3 mmol) and 1,4-dioxane (3 mL) was stirred at 100° C. for 3 h. The reaction was cooled to room temperature. The layers were separated and an aliquot of the basic potassium carbonate aqueous layer was analyzed by LCMS and showed that desired product was present. The aqueous layer was acidified using 1N aq HCl solution to pH˜6 by pH paper and was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification of the residue by silica gel chromatography (Analogix IF280, 0-10% MeOH/CH2Cl2, SF15-12 g, 20 min) followed by another purification (100% EtOAc for 10 min and then 0-8% MeOH/CH2Cl2 for 15 min) and finally subsequent purification by silica gel chromatography (Analogix IF280, SF15-4 g, Solvent A=EtOAc; Solvent B=10% MeOH/CH2Cl2; Gradient: 100% A for 10 min then ramped to 100% B over 20 min (i.e. 0-100% of B/A) provided the title product as a pale yellow solid (232 mg, 0.53 mmol, 69%). MS(ES)+ m/e 428.9 [M+H]+.

Quelle