Sodium Bicarbonate → 3,6-dihydro-2H-[4,4]bipyridinyl-1,3'-dicarboxylic acid 1-t-butyl ester 3'-methyl ester

HRID 41619

反応式

HRID 41619 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][O:24][C:25](=[O:33])[C:26]1[C:31](Br)=[CH:30][CH:29]=[N:28][CH:27]=1.C([O-])(O)=O.[Na+]>C1COCC1.O.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>[CH3:23][O:24][C:25]([C:26]1[CH:27]=[N:28][CH:29]=[CH:30][C:31]=1[C:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH:12]=1)=[O:33]

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 23436966Methyl 4-bromopyridine-3-carboxylate

生成物 1

HCID 584428293,6-dihydro-2H-[4,4]bipyridinyl-1,3'-dicarboxylic acid 1-t-butyl ester 3'-methyl ester収率 72.3%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
72 °C

実験手順

A solution of PdCl2(PPh3)2 (1.3 g, 1.9 mmol, 0.05 eq.) in THF (250 mL) was stirred for 10 minutes under nitrogen. 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (11.7 g, 37.8 mmol, 1.0 eq.) was added and the resulting solution was stirred for another 10 minutes. 4-Bromonicotinic acid methyl ester (8.2 g, 38.0 mmol, 1.0 eq.) in THF (100 mL) and NaHCO3 (16.1 g, 151.9 mmol, 4.0 eq.) in H2O (76 mL) were added, and the resulting solution was stirred for 6 hours while the temperature was maintained at 72° C. in an oil bath. The mixture was cooled to room temperature and the reaction was then quenched with water (50 mL). The resulting solution was extracted with EtOAc (150 mL). The organic layer was washed with saturated aqueous NaCl (3×200 mL), dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with EtOAc/PE (1:5) to yield 3,6-dihydro-2H-[4,4]bipyridinyl-1,3′-dicarboxylic acid 1-t-butyl ester 3′-methyl ester (8.7 g) as a white solid. ES m/z: [M+H]+319.

後処理

  1. stirringthe resulting solution was stirred for 6 hours while the temperature
  2. temperatureThe mixture was cooled to room temperature
  3. customthe reaction was then quenched with water (50 mL)
  4. extractionThe resulting solution was extracted with EtOAc (150 mL)
  5. washThe organic layer was washed with saturated aqueous NaCl (3×200 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under vacuum
  8. washeluted with EtOAc/PE (1:5)

出典と根拠

ORDレコード
ord-6c71bc7c51f9475abf192c5b52884042
出典データセット
uspto-grants-2013_09
特許番号
US08530663B2

関連ノート

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