Lithium Hexamethyldisilazide → (R)-3-((S,E)-2-(4-fluoro-3,5-dimethylbenzyl)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one

HRID 1158129노트

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HRID 1158129 반응식
[CH3:1][CH:2]([CH3:24])/[CH:3]=[CH:4]/[CH2:5][CH2:6][CH2:7][CH2:8][C:9]([N:11]1[C@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][C:12]1=[O:23])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([CH3:45])[C:43]=1[F:44])[CH2:39]Br>C1COCC1>[F:44][C:43]1[C:36]([CH3:35])=[CH:37][C:38]([CH2:39][C@H:8]([CH2:7][CH2:6][CH2:5]/[CH:4]=[CH:3]/[CH:2]([CH3:24])[CH3:1])[C:9]([N:11]2[C@H:15]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:14][O:13][C:12]2=[O:23])=[O:10])=[CH:41][C:42]=1[CH3:45]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 177507135-(Bromomethyl)-2-fluoro-1,3-dimethylbenzeneHCID 59512586(R)-3-((E)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one

생성물 1

HCID 59512601(R)-3-((S,E)-2-(4-fluoro-3,5-dimethylbenzyl)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one수율 68.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a cooled (−78° C.) solution of (R)-3-((E)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one (2.000 g, 6.071 mmol) in 40 mL of THF, was added LiHMDS (9.1 mL, 9.1 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (1.450 g, 6.678 mmol) in 10 mL of THF was added. After being stirred at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h, and then quenched with 80 mL of NH4Cl solution and extracted with dichloromethane (60 mL×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (1.925 g, 68% yield). GC-MS: tR=8.8 min; m/z 465 (M+).

후처리

  1. stirringAfter being stirred at −78° C. for 1 h the reaction mixture
  2. temperaturewas warmed to room temperature for 2 h
  3. customquenched with 80 mL of NH4Cl solution
  4. extractionextracted with dichloromethane (60 mL×3)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was isolated by Flash column chromatography (silica gel column)
  9. washeluting with 0-100% dichloromethane/hexanes

출처 및 근거

ORD 기록
ord-7d22810b2f6c470ebba722897d8a8e1e
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807720B2

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