3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → tert-Butyl 5'-bromo-3'h-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

HRID 1483924노트

반응식

HRID 1483924 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([CH2:9]Cl)[CH:3]=1.[Cl-].[Li+].C([Mg]Cl)(C)C.[C:18]([N:25]1[CH2:28][C:27](=[O:29])[CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[C:27]1([CH2:26][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:28]1)[O:29][CH2:9]2

참가 물질

5

반응물 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 706632554-Bromo-2-(chloromethyl)-1-iodobenzeneHCID 178461733HCID 178461733, 화합물

생성물 1

HCID 66555337tert-Butyl 5'-bromo-3'h-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate수율 77.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-15 °C

실험 절차

To a solution of 4-bromo-2-(chloromethyl)-1-iodobenzene (2.0 g, 6.04 mmol, 1 eq) in THF (16 mL), isopropylmagnesium chloride lithium chloride complex (5.11 mL, 1.3M in THF, 1.1 eq) was added over about 5 min while the internal temperature didn't exceed −15° C. Reaction is stirred at −15° C. for 30 min. Then a solution of 1-Boc-3-azetidinone (1.24 g, 1.2 eq) in THF (4 mL) was added dropwise; internal temperature at −30° C. The reaction is stirred at room temperature overnight. Reaction was quenched with a solution of citric acid (14 mL of 1M). This was extracted with MTBE and organic layer was washed with aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude yellow oil is submitted to silica gel column chromatography (0 to 50% ethyl acetate in heptane). 1.6 g of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate was obtained.

후처리

  1. customexceed −15° C
  2. customReaction
  3. customat −30° C
  4. stirringThe reaction is stirred at room temperature overnight
  5. customReaction
  6. customwas quenched with a solution of citric acid (14 mL of 1M)
  7. extractionThis was extracted with MTBE and organic layer
  8. washwas washed with aqueous NaHCO3 and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-956a7748ca794f8f9730a58dfc012ef4
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09420793B2

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