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 1177538노트

반응식

HRID 1177538 반응식
[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

참가 물질

4

반응물 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

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b7dbd7b05350405cb5e37708232cc0db
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842685B2

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