2,2-Difluoro-2-(fluorosulfonyl)acetic acid → Methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoate

HRID 2425485ノート

反応式

HRID 2425485 の反応式
[CH3:1][N:2]([CH3:27])[C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[C:20]([O:22][C@@H:23]([CH3:26])[CH2:24][OH:25])[CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[N:9][CH:10]=1)=[O:4].[F:28][C:29]([F:37])(S(F)(=O)=O)C(O)=O>C(#N)C.[Cu]I>[F:28][CH:29]([F:37])[O:25][CH2:24][C@@H:23]([O:22][C:20]1[CH:19]=[C:14]([CH:13]=[C:12]([O:11][C:8]2[CH:7]=[N:6][C:5]([C:3](=[O:4])[N:2]([CH3:1])[CH3:27])=[CH:10][N:9]=2)[CH:21]=1)[C:15]([O:17][CH3:18])=[O:16])[CH3:26]

参加物

5

反応物 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 59205095methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate

生成物 1

HCID 59205092Methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoate

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6342Acetonitrile溶媒2 回

反応条件

温度
55 °C

実験手順

A solution of methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate (94 g, 250 mmol) in acetonitrile (1130 mL) was degassed with nitrogen then copper(I) iodide (9.54 g, 50 mmol) was charged and the solution was heated to 55° C. A solution of 2,2-difluoro-2-fluorosulfonyl-acetic acid (CAS no. 1717-59-5) (46.6 mL, 450 mmol) in acetonitrile (188 mL) was charged dropwise. After 3 hours the solvent was evaporated under reduced pressure at 25° C. The residue was taken up in dichloromethane (500 mL) and filtered. The solid was washed further with dichloromethane until the washings were clear. The solvent was evaporated under reduced pressure at 25° C. and the residue was purified by flash chromatography eluting with 100% ethyl acetate to afford the title compound (54 g).

後処理

  1. customAfter 3 hours the solvent was evaporated under reduced pressure at 25° C
  2. filtrationfiltered
  3. washThe solid was washed further with dichloromethane until the washings
  4. customThe solvent was evaporated under reduced pressure at 25° C.
  5. customthe residue was purified by flash chromatography
  6. washeluting with 100% ethyl acetate

出典と根拠

ORDレコード
ord-34576ba338f8449fa742843c267b8b19
出典データセット
uspto-grants-2011_06
特許番号
US07964725B2

反応ノート

読み込み中…