Aluminium lithium hydride → 4-[((S)-4,4-difluoro-pyrrolidin-2-ylmethyl)-amino]-adamantan-1-ol

HRID 1644806ノート

反応式

HRID 1644806 の反応式
[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH:11]3[NH:18][C:19]([C@@H:21]3[CH2:25][C:24]([F:27])([F:26])[CH2:23][NH:22]3)=O)[CH2:9]1)[CH2:15]2>C1COCC1>[F:27][C:24]1([F:26])[CH2:23][NH:22][C@H:21]([CH2:19][NH:18][CH:11]2[CH:12]3[CH2:17][C:8]4([OH:7])[CH2:15][CH:14]([CH2:16][CH:10]2[CH2:9]4)[CH2:13]3)[CH2:25]1

参加物

4

反応物 2

HCID 21226445Aluminium lithium hydrideHCID 66773511(S)-4,4-difluoro-pyrrolidine-2-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide

生成物 1

HCID 667745474-[((S)-4,4-difluoro-pyrrolidin-2-ylmethyl)-amino]-adamantan-1-ol収率 43.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Lithium aluminium hydride (0.51 g) was added in portions to the solution of (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide (1.2 g) in THF (15 mL) at RT. The reaction mixture was refluxed for 24 h. The reaction mixture was quenched with saturated aqueous sodium sulfate solution (15 mL) at 0° C., filtered through Celite® and extracted with ethyl acetate (3×10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under high vacuum using rotary evaporator to give a crude material, which was purified through column chromatography (3% MeOH:DCM, silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 7 inch) to afford the desired 4-[((S)-4,4-difluoro-pyrrolidin-2-ylmethyl)-amino]-adamantan-1-ol as a white solid (0.5 g).

後処理

  1. temperatureThe reaction mixture was refluxed for 24 h
  2. customThe reaction mixture was quenched with saturated aqueous sodium sulfate solution (15 mL) at 0° C.
  3. filtrationfiltered through Celite®
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under high vacuum
  7. customevaporator
  8. customto give a crude material, which
  9. customwas purified through column chromatography (3% MeOH:DCM, silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 7 inch)

出典と根拠

ORDレコード
ord-7c85ee80537b4f82a7570370869ce7c9
出典データセット
uspto-grants-2012_02
特許番号
US08124636B2

反応ノート

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