Diisopropylethylamine → Methyl 6-(2,6-difluoro-4-(2-hydroxypropan-2-yl)phenyl)-5-fluoropicolinate
反応式
[F:1][C:2]1[CH:3]=[C:4]([C:18]([OH:21])([CH3:20])[CH3:19])[CH:5]=[C:6]([F:17])[C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:23]1[N:28]=[C:27]([C:29]([O:31][CH3:32])=[O:30])[CH:26]=[CH:25][C:24]=1[F:33].CCN(C(C)C)C(C)C>O1CCOCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:17][C:6]1[CH:5]=[C:4]([C:18]([OH:21])([CH3:19])[CH3:20])[CH:3]=[C:2]([F:1])[C:7]=1[C:23]1[N:28]=[C:27]([C:29]([O:31][CH3:32])=[O:30])[CH:26]=[CH:25][C:24]=1[F:33]参加物
反応物 3
生成物 1
試薬・触媒・溶媒 3
反応条件
- 温度
- 120 °C
実験手順
To a nitrogen purged mixture of 2-[3,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propan-2-ol (1.53 g, 5.13 mmol), methyl 6-bromo-5-fluoropyridine-2-carboxylate (1.20 g, 5.13 mmol) and DIPEA (2.7 mL, 15 mmol) in 1,4-dioxane (20 mL) and water (1.2 mL), bis(tri-tert-butylphosphine)palladium (262 mg, 0.513 mmol) was added. The reaction mixture was heated at 120° C. for 40 min., then cooled and filtered through a pad of diatomaceous earth. The filtrate was concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (0-50% EtOAc in hexanes) to give methyl 6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxylate as a white powder, which was used without further purification.
後処理
- customTo a nitrogen purged
- additionwas added
- temperaturecooled
- filtrationfiltered through a pad of diatomaceous earth
- concentrationThe filtrate was concentrated under reduced pressure
- customThe crude residue was purified by silica gel column chromatography (0-50% EtOAc in hexanes)
出典と根拠
- ORDレコード
- ord-a4d2cd6192e846ebb1974b468c6fcc8f
- 出典データセット
- uspto-grants-2015_12
- 特許番号
- US09200004B2
反応ノート
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