반응 #43801

반응 방정식

EtOH

2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane

6-bromopicolinic acid

Na2CO3

→

desired product

수율 46.0%

6-(4-Fluorophenyl)picolinic acid

수율 46.0%

용매

DME

반응 조건

후처리

1. 1
   기타the mixture was purged with Ar gas
2. 2
   workup.ADDITIONAdditional 2-bromopicolinic acid (900 mg) and Pd (OAc)2 was added
3. 3
   기타after purging with Ar gas it
4. 4
   온도was heated at 100° C. for 4.5 h
5. 5
   workup.ADDITIONTrifluoroacteic acid (20 mL) was added to the reaction mixture
6. 6
   농축concentrated
7. 7
   workup.ADDITIONMeOH (150 mL) was added to the residue
8. 8
   여과The insoluble material was filtered
9. 9
   농축the filtrate solution was concentrated
10. 10
    기타Purification by flash column on silica gel eluting with EtOAc/MeOH//900:100

실험 절차

A solution of 6-bromopicolinic acid (Aldrich) (2.02 g, 10 mmol) in DME containing 4 mL of 10% aq Na2CO3 was purged with Ar gas. To this mixture was added Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane (2.40 g, 11.5 mmol, Wako Pure Chemical Industries, Ltd) and EtOH (20 mL), and the mixture was purged with Ar gas. The reaction mixture was heated at 100° C. for 2.5 h in a sealed tube. Additional 2-bromopicolinic acid (900 mg) and Pd (OAc)2 was added, and after purging with Ar gas it was heated at 100° C. for 4.5 h. Trifluoroacteic acid (20 mL) was added to the reaction mixture, concentrated and MeOH (150 mL) was added to the residue. The insoluble material was filtered, and the filtrate solution was concentrated. Purification by flash column on silica gel eluting with EtOAc/MeOH//900:100 followed by EtOAc/MeOH/HOAc//700:1500:50 provided the desired product (1.0 g, 40% based on borinane starting material) as a white solid. 1H NMR (CD3OD) δ 8.01 (d, 1H, J=7.7 Hz), 7.94-7.87 (m, 3H), 7.73 (d, 1H, J=7.7 Hz), 7.13 (t, 2H, 8.8 Hz); MS(ESI+) m/z 234 (M+H)+.

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