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Sodium borohydride → tert-butyl 4-(3-amino-6-((1R,3R,4R)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596021
ノート
印刷プレビュー

反応式

HRID 596021 の反応式
[NH2:1][C:2]1[C:3]([C:16]2[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[C:18]([F:29])[CH:17]=2)=[N:4][C:5]([C@@H:8]2[CH2:13][CH2:12][C:11](=[O:14])[C@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1.[BH4-].[Na+]>CO>[NH2:1][C:2]1[C:3]([C:16]2[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])=[C:18]([F:29])[CH:17]=2)=[N:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1.[NH2:1][C:2]1[C:3]([C:16]2[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])=[C:18]([F:29])[CH:17]=2)=[N:4][C:5]([C@@H:8]2[CH2:13][CH2:12][C@@H:11]([OH:14])[C@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 4311764Sodium borohydrideHCID 118049846(+/-)-tert-butyl 4-(3-amino-6-((1R,3R)-3-fluoro-4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

生成物 2

HCID 118045246tert-butyl 4-(3-amino-6-((1R,3R,4R)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate収率 47%HCID 118045514(+/-)-tert-butyl 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate収率 43.9%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of (+/−)-tert-butyl 4-(3-amino-6-((1R,3R)-3-fluoro-4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (1.9 g, 4.71 mmol) in MeOH (47.1 mL) was added NaBH4 (0.267 g, 7.06 mmol) at 0° C. The reaction mixture was stirred for 2 h. After quenched with sat. NaHCO3 solution, the reaction mixture was extracted with EtOAc. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography eluting with flat 35% of EtOAc in heptane to provide (+/−)-tert-butyl 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (839 mg, 2.07 mmol, 43.9%) and (+/−)-tert-butyl 4-(3-amino-6-((1R,3R,4R)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (900 mg, 2.22 mmol, 47%). LCMS (m/z): 406.3 (MH+), 0.85 min and 406.3 (MH+), 0.85 min respectively.

後処理

  1. customAfter quenched with sat. NaHCO3 solution
  2. extractionthe reaction mixture was extracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography
  8. washeluting with flat 35% of EtOAc in heptane

出典と根拠

ORDレコード
ord-fa288fce9fa64dae8a97928a674f91b9
出典データセット
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09242996B2

反応ノート

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