Aluminium lithium hydride → (2S,4S)-tert-butyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 1177538ノート

反応式

HRID 1177538 の反応式
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1[CH:9]=[C:10]([C:32]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:34]([C:44](OC)=[O:45])[CH:33]=2)[CH:11]=[CH:12][C:13]=1[C:14]1[S:15][C:16]2[C:21]([N:22]=1)=[CH:20][CH:19]=[C:18]([C:23]1([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:25][CH2:24]1)[N:17]=2>C1COCC1>[F:7][C:8]1[CH:9]=[C:10]([C@H:32]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[C@H:34]([CH2:44][OH:45])[CH2:33]2)[CH:11]=[CH:12][C:13]=1[C:14]1[S:15][C:16]2[C:21]([N:22]=1)=[CH:20][CH:19]=[C:18]([C:23]1([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:25][CH2:24]1)[N:17]=2

参加物

4

反応物 2

HCID 21226445Aluminium lithium hydrideHCID 67112968(2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate

生成物 1

HCID 67111989(2S,4S)-tert-butyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of lithium aluminum hydride, 1.0 M solution in tetrahydrafuran (1.165 mL, 1.165 mmol) in 7 mL THF at 0° C. was added a solution of (S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate (0.555 g, 0.971 mmol) dropwise via syringe, over 5 min. The reaction mixture became a deep purple color. The bath was removed, and after 30 min, the reaction mixture was re-cooled, and treated with ice carefully. 6 mL 1N aq. HCl was added and the aq. Layer was extracted with DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel chromatography, 0-100% EA/hexanes gradient gave (2S,4S)-tert-butyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxylate. MS (ESI) m/z: Calculated: 545.2; Observed: 546.1 (M++1).

後処理

  1. customThe bath was removed
  2. waitafter 30 min
  3. temperaturethe reaction mixture was re-cooled
  4. additiontreated with ice carefully
  5. addition6 mL 1N aq. HCl was added
  6. extractionthe aq. Layer was extracted with DCM
  7. dry with materialThe combined organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel chromatography, 0-100% EA/hexanes gradient

出典と根拠

ORDレコード
ord-b7dbd7b05350405cb5e37708232cc0db
出典データセット
uspto-grants-2010_11
特許番号
US07842685B2

反応ノート

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