Diisopropylethylamine → (3R,4R)-benzyl 3-(((S)-2-acetoxy-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate

HRID 404853ノート

反応式

HRID 404853 の反応式
[CH2:1]([C:8]1[O:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[CH:21]([NH:26][CH2:27][C@H:28]1[C@@H:32]([F:33])[CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:29]1)[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:53]([O:56][C@@H:57]([CH3:61])[C:58](Cl)=[O:59])(=[O:55])[CH3:54]>ClCCl>[C:53]([O:56][C@@H:57]([CH3:61])[C:58]([N:26]([CH2:27][C@H:28]1[C@@H:32]([F:33])[CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[O:35])[CH2:29]1)[C@@H:21]([C:9]1[N:10]=[C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])[O:12][C:8]=1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:59])(=[O:55])[CH3:54]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 86693896(+/-)-(3R,4R)-benzyl 3-((1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate

生成物 1

HCID 86693897(3R,4R)-benzyl 3-(((S)-2-acetoxy-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate収率 17%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (±)-(3R,4R)-benzyl 3-((1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate (37 mg, 0.063 mmol) in dichloromethane (0.63 mL, 0.1 M solution) at room temperature was added N,N-diisopropylethylamine (55 μL, 0.313 mmol). (S)-1-Chloro-1-oxopropan-2-yl acetate (15.8 μL, 0.125 mmol) was then added dropwise over 2 min. The resulting solution was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Two diastereomers were separated on preparative TLC (2% MeOH in dichloromethane). The polar diastereomer, (3R,4R)-benzyl 3-(((S)-2-acetoxy-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate, was obtained in 17% yield (7.5 mg). LC/MS (uplc): MH+ 706.4, 1.34 min. The nonpolar diastereomer, (3R,4R)-benzyl 3-(((S)-2-acetoxy-N—((S)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate, was obtained in 16% yield (7.0 mg). LC/MS (uplc): MH+ 706.4, 1.35 min.

後処理

  1. customThe reaction mixture was quenched with saturated NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customTwo diastereomers were separated on preparative TLC (2% MeOH in dichloromethane)

出典と根拠

ORDレコード
ord-748bb2c240db445daf8fd1875af8864c
出典データセット
uspto-grants-2014_06
特許番号
US08748626B2

反応ノート

読み込み中…