Diisopropylamine → Methyl 5-(4-fluorophenyl)-6-hydroxynicotinate

HRID 1909151ノート

反応式

HRID 1909151 の反応式
Br[C:2]1[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[Na+].O.S(C1C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=CC=1)([O-])(=O)=O.[Na+].[Na+].C(NC(C)C)(C)C>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=2)=[CH:16][CH:15]=1

参加物

8

反応物 4

HCID 7912DiisopropylamineHCID 2856454-Fluorophenylboronic acidHCID 2764315Methyl 5-bromo-6-hydroxynicotinateHCID 53487040Sodium 3,3',3''-phosphinetriyltribenzenesulfonate hydrate

生成物 1

HCID 67339481Methyl 5-(4-fluorophenyl)-6-hydroxynicotinate収率 65.5%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
125 °C

実験手順

To a solution of methyl 5-bromo-6-oxo-1,6-dihydropyridine-3-carboxylate (0.5 g, 2.16 mmol) in DMF (8.1 mL) and water (2.7 mL) were added (4-fluorophenyl)boronic acid (0.38 g, 2.69 mmol), palladium(II)acetate (36.3 mg, 0.16 mmol), tris(3-sulfonatophenyl)phosphine hydrate sodium salt (0.31 g, 0.49 mmol) and diisopropylamine (1.54 mL, 10.77 mmol). The mixture was heated in the microwave reactor for 15 min at 125° C. The mixture was filtered and water was added to the filtrate. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→70% dichloromethane/ethyl acetate) gave the title compound (0.35 g). MS 248.1 (M+1).

後処理

  1. filtrationThe mixture was filtered
  2. additionwater was added to the filtrate
  3. extractionThe mixture was extracted with ethyl acetate (3×)
  4. washThe combined organic extracts were washed with water (3×), brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% dichloromethane→70% dichloromethane/ethyl acetate)

出典と根拠

ORDレコード
ord-4c9043255e504be898c1ce263e88a52b
出典データセット
uspto-grants-2013_12
特許番号
US08598209B2

反応ノート

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