2,2-Difluoro-2-(fluorosulfonyl)acetic acid → (2S,4S)-1-tert-butyl 2-methyl 4-((difluoromethoxy)methyl)pyrrolidine-1,2-dicarboxylate

HRID 1413010ノート

反応式

HRID 1413010 の反応式
[OH:1][CH2:2][C@@H:3]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1.[F:19][C:20]([F:28])(S(F)(=O)=O)C(O)=O>[Cu]I.C(#N)C>[F:19][CH:20]([F:28])[O:1][CH2:2][C@@H:3]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9])[C@H:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1

参加物

5

反応物 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 696750381-(1,1-Dimethylethyl) 2-methyl (2S,4S)-4-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate

生成物 1

HCID 69672725(2S,4S)-1-tert-butyl 2-methyl 4-((difluoromethoxy)methyl)pyrrolidine-1,2-dicarboxylate収率 61%

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

反応条件

温度
45 °C

実験手順

A 100 mL round-bottom flask was charged with (2S,4S)-1-tert-butyl 2-methyl 4-(hydroxymethyl)pyrrolidine-1,2-dicarboxylate (3.33 g, 12.84 mmol), CuI (0.489 g, 2.56 mmol), and anhydrous acetonitrile (57.1 mL). The reaction was heated to 45° C. (ext. oil bath). 2,2-difluoro-2-(fluorosulfonyl)acetic acid (2.655 mL, 25.68 mmol) was added at 45° C. over 30 minutes via syringe pump. The reaction was heated for 30 minutes. Upon completion as monitored by TLC, the reaction mixture was cooled to room temperature and concentrated in vacuo. The crude residue was diluted in EtOAc and washed with sodium bicarbonate (aq). The bicarbonate layer was back extracted with ethyl acetate twice. Combined organic layers were washed with brine, dried over sodium sulphate, filtered and concentrated. The resulting residue was further purified via silica gel chromatography (10 to 40% EtOAc/Hexanes) to afford (2S,4S)-1-tert-butyl 2-methyl 4-((difluoromethoxy)methyl)pyrrolidine-1,2-dicarboxylate (2.41 g, 61%). MS (ESI) m/z 210.21 [M+H-Boc]+.

後処理

  1. temperatureThe reaction was heated for 30 minutes
  2. temperaturethe reaction mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. additionThe crude residue was diluted in EtOAc
  5. washwashed with sodium bicarbonate (aq)
  6. extractionThe bicarbonate layer was back extracted with ethyl acetate twice
  7. washCombined organic layers were washed with brine
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue was further purified via silica gel chromatography (10 to 40% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-ba89faf119284129963d18253465802c
出典データセット
uspto-grants-2014_12
特許番号
US08921341B2

反応ノート

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