Lithium Hexamethyldisilazide → Methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarboxylate

HRID 1930134노트

반응식

HRID 1930134 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:12][CH2:13][CH2:14][CH:15]([C:20]1[CH:25]=[CH:24][C:23]([B:26]2[O:30][C:29]([CH3:32])([CH3:31])[C:28]([CH3:34])([CH3:33])[O:27]2)=[C:22]([Cl:35])[CH:21]=1)[C:16]([O:18][CH3:19])=[O:17]>C1COCC1>[Cl:35][C:22]1[CH:21]=[C:20]([C:15]2([C:16]([O:18][CH3:19])=[O:17])[CH2:14][CH2:13][CH2:12]2)[CH:25]=[CH:24][C:23]=1[B:26]1[O:30][C:29]([CH3:32])([CH3:31])[C:28]([CH3:34])([CH3:33])[O:27]1

참가 물질

4

반응물 2

HCID 2733832Lithium HexamethyldisilazideHCID 59627651Methyl 5-bromo-2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanoate2회

생성물 1

HCID 59627692Methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarboxylate수율 98.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

Lithium bis(trimethylsilyl)amide (0.872 mL, 0.87 mmol) was added dropwise to methyl 5-bromo-2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanoate (Intermediate 7-3; 342 mg, 0.79 mmol) in THF (10 mL) cooled to 0° C. under nitrogen the reaction and was stirred at 0° C. for 12 hours. The reaction mixture was quenched with saturated NH4Cl (50 mL) and was diluted with EtOAc (75 mL). The organic layer was separated and re-extracted with EtOAc (75 mL). The combined organics were washed with saturated brine (50 mL), dried (MgSO4), filtered and concentrated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarboxylate (273 mg, 98%) as a colourless gum.

후처리

  1. customthe reaction
  2. customThe reaction mixture was quenched with saturated NH4Cl (50 mL)
  3. additionwas diluted with EtOAc (75 mL)
  4. customThe organic layer was separated
  5. extractionre-extracted with EtOAc (75 mL)
  6. washThe combined organics were washed with saturated brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford crude product
  11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane
  12. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-95c714dc4a2c4adaabb6d949be56cb73
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188092B2

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