Dimethylformamide → Methyl 5-cyano-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate

HRID 1820970ノート

反応式

HRID 1820970 の反応式
Cl[C:2]1[C:3]([O:12][CH:13]([CH3:18])[C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH3:19][N:20](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:19]([C:2]1[C:3]([O:12][CH:13]([CH3:18])[C:14]([F:17])([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:20]

参加物

6

反応物 2

HCID 6228DimethylformamideHCID 68852290Methyl 5-chloro-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate

生成物 1

HCID 68850684Methyl 5-cyano-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
120 °C

実験手順

To a solution of 627 mg (2.21 mmol) of methyl 5-chloro-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate (from Step B), 123 mg (0.22 mmol), 156 mg (1.33 mmol) of zinc cyanide, and 29 mg (0.44 mmol) of zinc dust in 5.0 ml of DMF was added 101 mg (0.11 mmol) of tris(dibenzylideneacetone)dipalladium(0). After stirring at 120° C. overnight, the mixture was filtered through a cake of Celite and washed with EtOAc. The filtrate was washed with brine (10 mL), H2O (3×10 mL), and brine (10 mL). The organic layer was dried over MgSO4 and concentrated. Chromatography on a Biotage 40M cartridge using 1:9 v/v EtOAc/hexanes as the eluant gave 498 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.59 (d, J=6.6, 3H), 3.97 (s, 3H), 5.93 (m, 1H), 8.54 (d, J=2.2, 1H), 8.96 (d, J=2.3, 1H).

後処理

  1. filtrationthe mixture was filtered through a cake of Celite
  2. washwashed with EtOAc
  3. washThe filtrate was washed with brine (10 mL), H2O (3×10 mL), and brine (10 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-d36eb1b78acf42dcb0810af5c3720bed
出典データセット
uspto-grants-2009_10
特許番号
US07605171B2

反応ノート

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