Lithium diisopropylamide → tert-butyl 4-[[2-[[(2S)-2-bicyclo[2.2.1]heptanyl]amino]-5-methyl-4-oxo-1,3-thiazol-5-yl]methyl]piperidine-1-carboxylate

HRID 852796

반응식

HRID 852796 반응식
[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[S:10][CH:11]([CH3:15])[C:12](=[O:14])[N:13]=1.C([N-]C(C)C)(C)C.[Li+].[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([CH2:37]Br)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[S:10][C:11]([CH2:37][CH:34]2[CH2:35][CH2:36][N:31]([C:29]([O:28][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:30])[CH2:32][CH2:33]2)([CH3:15])[C:12](=[O:14])[N:13]=1

참가 물질

5

반응물 3

HCID 2724682Lithium diisopropylamideHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 178435106HCID 178435106, 화합물

생성물 1

HCID 178451850tert-butyl 4-[[2-[[(2S)-2-bicyclo[2.2.1]heptanyl]amino]-5-methyl-4-oxo-1,3-thiazol-5-yl]methyl]piperidine-1-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a solution of 2-((2S)-bicyclo[2.2.1]heptan-2-ylamino)-5-methylthiazol-4(5H)-one in anhydrous THF (30 mL) at −78° C. under N2 was added lithium diisopropylamide (Aldrich, 2.0 M in heptane/THF/ethylbenzene, 9.2 mL, 18.4 mmol). After stirring the reaction mixture at −78° C. for 1 h, a solution of 4-bromomethyl-piperidine-1-carboxylic acid tert-butyl ester (Pharma Core, 5.12 g, 18.4 mmol, 4.0 eq) in anhydrous THF (10 mL) was added under N2. The resulting reaction mixture was stirred at −78° C. for 4 h. The cooling bath was removed, and the reaction mixture was stirred at ambient temperature for ca. 18 h. Saturated NH4Cl was then added, and the THF was removed in vacuo. The residue was extracted with EtOAc (3×180 mL), and the combined organic layers were washed with saturated NaCl, dried over Na2SO4, filtered, and concentrated in vacuo. Flash column chromatography (silica gel, 0-60% EtOAc in hexane) afforded the title compound as an off-white solid (1.42 g). MS (ESI, neg. ion) m/z: 420 (M−H).

후처리

  1. customThe resulting reaction mixture
  2. stirringwas stirred at −78° C. for 4 h
  3. customThe cooling bath was removed
  4. stirringthe reaction mixture was stirred at ambient temperature for ca. 18 h
  5. additionSaturated NH4Cl was then added
  6. customthe THF was removed in vacuo
  7. extractionThe residue was extracted with EtOAc (3×180 mL)
  8. washthe combined organic layers were washed with saturated NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-9e3ec1b110c449f0874fc311739c9969
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07253196B2

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