Cholesterol → Glycidyl cholesterol

HRID 216995

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HRID 216995 반응식
[CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[CH3:29][C:30](C)([O-:32])[CH3:31].[Li+].C(C1OC1)Br>CN(C)C(=O)C>[CH2:29]([CH2:3][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:1])[CH:30]1[O:32][CH2:31]1

참가 물질

5

반응물 3

HCID 5997CholesterolHCID 18430EpibromohydrinHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

생성물 1

HCID 86601307Glycidyl cholesterol수율 64%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
10 °C

실험 절차

Cholesterol (5.80 g; 15 mmol; Sigma, St. Louis, Mo.) was dissolved in 76 ml dry N,N-dimethylacetamide (DMAc) under a flow of dry argon. The solution was cooled to 10° C. and 15 ml (15 mmol) of a 1.0M solution of lithium tert-butoxide in hexanes (Sigma) was added. After further cooling to 5° C., 10 ml (117 mmol) of freshly distilled epibromohydrin was added and the mixture was stirred at 3-5° C. for 2 hours. The temperature was allowed to slowly rise to 21-23° C. and the reaction was allowed to continue for another hour. The reaction mixture was then diluted with 500 ml of 0.5% aqueous KHCO3 and extracted with 350 ml n-heptane and then twice more with 100 ml n-heptane. The combined organic layers were dried over Na2SO4. After filtration from the desiccant, the solvent was removed in vacuo. The syrupy residue (7.3 g) was purified by flash-chromatography on silica gel employing elution with hexane, hexane/toluene (1:1 mixture), and toluene. The fractions containing pure glycidyl-cholesterol (thin layer chromatography (TLC)-monitoring) were pooled and dried in vacuo until crystallization occurred. The procedure yielded 4.25 g glycidyl-cholesterol (64%). The product displayed an Rf of 0.38 by TLC (silica gel, n-heptane/ethyl acetate, 85:15 by volume). The signals (only those produced by the glycidyl group not present in the starting cholesterol) obtained by 1H NMR analysis of the product are as follows: 2.62 and 2.87 (both m, 1H and 1H, two non-equivalent H of oxirane CH2), 3.15 (m, 1H, CH), and 3.47 and 3.72 (both m, 1H and 1H, diastereotopic H of CH2O).

후처리

  1. temperatureAfter further cooling to 5° C.
  2. customto slowly rise to 21-23° C.
  3. waitto continue for another hour
  4. extractionextracted with 350 ml n-heptane
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationAfter filtration from the desiccant
  7. customthe solvent was removed in vacuo
  8. customThe syrupy residue (7.3 g) was purified by flash-chromatography on silica gel employing elution with hexane, hexane/toluene (1:1 mixture), and toluene
  9. additionThe fractions containing pure glycidyl-cholesterol (thin layer chromatography (TLC)-monitoring)
  10. customdried in vacuo until crystallization

출처 및 근거

ORD 기록
ord-78e09dded4224e57bd7945d9535fecad
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193290B2

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