Ethanol → (3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrile

HRID 893797ノート

反応式

HRID 893797 の反応式
[H-].[Na+].Br[C@H:4]1[C@H:9](O)[C:8]2[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:7]=2[O:6][C:5]1([CH3:18])[CH3:17].C(O)C.[OH-:22].[NH4+:23]>O1CCCC1>[NH2:23][C@@H:9]1[C:8]2[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:7]=2[O:6][C:5]([CH3:18])([CH3:17])[C@H:4]1[OH:22]

参加物

6

反応物 4

HCID 702EthanolHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 6932483trans-2,2-Dimethyl-3-bromo-6-cyanochroman-4-ol

生成物 1

HCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrile

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Sodium hydride (80% dispersion in oil, 13.7 g) was added in portions over 1 h to a stirred solution of (±)-trans-3-bromo-6-cyano-3,4-dihydro-2,2-dimethyl-2H-benzopyran-4-ol (124.3 g) in tetrahydrofuran (250 ml) kept under a dry nitrogen atmosphere. The mixture was stirred for an additional 0.5 h after which a solution of the 3,4-epoxide resulted. Ethanol (620 ml) followed by 0.880 ammonium hydroxide (375 ml) were added, and the resulting mixture stirred at 60°-65° C. for 12 h before cooling to room temperature. The organic solvents were evaporated off and the aqueous residue acidified with 5N hydrochloric acid (125 ml). The mixture was then washed well with dichloromethane (total used=1.0 L) before basifying with 40% aq. sodium hydroxide (80ml). It was then re-extracted with dichloromethane (4×250 ml) and the combined extracts washed once with brine and then dried (Na2SO4). Evaporation afforded the product as a gum which crystallised. This was broken up and triturated with a mixture of isopropyl ether and dichloromethane before filtering off and washing with further isopropyl ether. The product was dried under suction and finally under vacuum.

後処理

  1. customresulted
  2. additionwere added
  3. customThe organic solvents were evaporated off
  4. washThe mixture was then washed well with dichloromethane (total used=1.0 L)
  5. extractionIt was then re-extracted with dichloromethane (4×250 ml)
  6. washthe combined extracts washed once with brine
  7. dry with materialdried (Na2SO4)
  8. customEvaporation

出典と根拠

ORDレコード
ord-9daa48b6e0a9411381f30531e8de0543
出典データセット
uspto-grants-1992_06
特許番号
US05126460

反応ノート

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