Tetrahydrofuran → HCID 59201437, 화합물

HRID 451878노트

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HRID 451878 반응식
C1(OC(=O)[CH2:9][CH2:10][C@@H:11]([CH2:27][O:28]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:12][C@H:13]2[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[N:14]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])CCCCC1.C[Mg]Br.[CH2:43]1[CH2:47]OC[CH2:44]1>>[CH3:44][C:43]1([CH3:47])[O:28][CH2:27][C@@H:11]([CH2:12][C@H:13]2[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[N:14]2[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:10][CH2:9]1

참가 물질

5

반응물 4

HCID 8028TetrahydrofuranHCID 59201488HCID 59201488, 화합물HCID 178418573HCID 178418573, 화합물HCID 178418689HCID 178418689, 화합물

생성물 1

HCID 59201437HCID 59201437, 화합물수율 78%

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온도
0 °C

실험 절차

The (S)-tert-butyl 4-((R)-5-(cyclohexyloxy)-5-oxo-2-(tosyloxymethyl)pentyl)-2,2-dimethyloxazolidine-3-carboxylate (309 mg, 0.545 mmol, 1.0 equiv) was dissolved in 17 mL of THF and the solution cooled to 0° C. Methylmagnesiumbromide (3.0 M in THF, 1.64 mL, 3.0 equiv) was added via syringe. LC/MS analysis showed ca 15% conversion to the mono-tosylate. An additional 0.55 mL of MeMgBr solution was added and the mixture warmed to ambient and stirred overnight. LC/MS analysis showed complete conversion to the mono-tosylate. The mixture was heated to reflux for 24 hr. After this time, complete conversion to the cyclised product was observed. The mixture was cooled to ambient and quenched with water. The layers were separated and the organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The pyran derivative was purified by flash chromatography on silica, (12 g), eluting with 0-41% EtOAc in hexanes. This afforded 138 g (78% yield) of (S)-tert-butyl 4-(((R)-6,6-dimethyl-tetrahydro-2H-pyran-3-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate as a clear syrup. MS ESI +ve m/z 350 (M+Na).

후처리

  1. temperaturethe mixture warmed
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 24 hr
  4. temperatureThe mixture was cooled to ambient and
  5. customquenched with water
  6. customThe layers were separated
  7. washthe organic layer washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe pyran derivative was purified by flash chromatography on silica, (12 g)
  12. washeluting with 0-41% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-d2181287a45f43b0b8b1827a9bc22f86
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08487108B2

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