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2,4-Dibromo-1-fluorobenzene → (+/-)-(3aR*,7aS*)-7a-(5-bromo-2-fluorophenyl)-hexahydropyrano[3,4-c]isoxazole

HRID 217998
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HRID 217998 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4](Br)[CH:3]=1.C([Li])CCC.[N:15]1[O:16][CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][C:19]=12>C1(C)C=CC=CC=1.C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([C@:19]23[CH2:20][O:21][CH2:22][CH2:23][C@H:18]2[CH2:17][O:16][NH:15]3)[CH:3]=1
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참가 물질

5

반응물 3

HCID 150342,4-Dibromo-1-fluorobenzeneHCID 574756753,3a,4,5-tetrahydro-7H-pyrano[3,4-c]isoxazoleHCID 178418339Butyllithium

생성물 1

HCID 59281218(+/-)-(3aR*,7aS*)-7a-(5-bromo-2-fluorophenyl)-hexahydropyrano[3,4-c]isoxazole

시약·촉매·용매 1

HCID 22635083Tetrahydrofuran toluene용매2회

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온도
-78 °C

실험 절차

1,3-Dibromo-4-fluorobenzene (837 mg) was dissolved in a toluene-THF (10:1) mixture (15 ml). The mixture was cooled to −78° C. and n-butyllithium (2.64 M, 1.19 ml) was added dropwise. After stirring at the same temperature for one hour, a solution of (±)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c]isoxazole obtained in Preparation Example 1-(2) (200 mg) in toluene-THF (10:1) (5.0 ml) and a boron trifluoride-diethyl ether complex (394 μl) were added dropwise at the same time. After stirring at the same temperature for three hours, the reaction was terminated with an ammonium chloride solution. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (365 mg).

후처리

  1. additiona boron trifluoride-diethyl ether complex (394 μl) were added dropwise at the same time
  2. stirringAfter stirring at the same temperature for three hours
  3. customthe reaction was terminated with an ammonium chloride solution
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe organic layer was washed with water and brine
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-1d6841f74bc844ed9f0bc8cc83fddfb0
출처 데이터셋
uspto-grants-2012_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08198269B2

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