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 2425482ノート

反応式

HRID 2425482 の反応式
[F:1][C:2]([F:10])(S(F)(=O)=O)C(O)=O.[CH3:11][N:12]([CH3:37])[C:13]([C:15]1[N:16]=[CH:17][C:18]([O:21][C:22]2[CH:23]=[C:24]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:36])[CH2:34][OH:35])[CH:31]=2)[C:25]([O:27][CH3:28])=[O:26])=[N:19][CH:20]=1)=[O:14]>C(#N)C.[Cu]I>[F:1][CH:2]([F:10])[O:35][CH2:34][C@@H:33]([O:32][C:30]1[CH:29]=[C:24]([CH:23]=[C:22]([O:21][C:18]2[CH:17]=[N:16][C:15]([C:13](=[O:14])[N:12]([CH3:11])[CH3:37])=[CH:20][N:19]=2)[CH:31]=1)[C:25]([O:27][CH3:28])=[O:26])[CH3:36]

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収率 62%

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

実験手順

2,2-Difluoro-2-fluorosulfonyl-acetic acid (CAS no. 1717-59-5) (0.84 mL, 8.05 mmol) in acetonitrile (20 mL) was added with a syringe pump dropwise over 90 minutes to a degassed stirring mixture of methyl 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(2S)-1-hydroxypropan-2-yl]oxy-benzoate (1.5 g, 22.0 mmol) and copper (I) iodide (154 mg, 4.55 mmol) in acetonitrile (300 mL) at 55° C. The volatiles were removed under reduced pressure and the residue taken up in DCM. The mixture was filtered to and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 25%-100% ethyl acetate in isohexane to afford the product (16.5 g, 62%). 1H NMR δ (CDCl3): 1.38 (3H, d), 3.15 (3H, s), 3.18 (3H, s), 3.91 (3H, s), 3.93-4.05 (2H, m), 4.62-4.68 (1H, m), 6.27 (1H, t), 6.95 (1H, t), 7.44-7.45 (1H, m), 7.49-7.51 (1H, m), 8.36 (1H, s), 8.53 (1H, s); m/z 404 (M+H+)

後処理

  1. customThe volatiles were removed under reduced pressure
  2. filtrationThe mixture was filtered to and the solvent
  3. customwas removed under reduced pressure
  4. customThe residue was purified by flash chromatography on silica
  5. washeluting with a gradient of 25%-100% ethyl acetate in isohexane

出典と根拠

ORDレコード
ord-9380124d0f054a0c9fd698ae60baf855
出典データセット
uspto-grants-2011_06
特許番号
US07964725B2

反応ノート

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