Boron trifluoride etherate → (R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3-hydroxypropene

HRID 744155노트

반응식

HRID 744155 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH:16]=[CH:17][C:18](OCC)=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(F)(F)F.CCOCC.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH:16]=[CH:17][CH2:18][OH:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 8000Boron trifluoride etherateHCID 21225700DiisobutylaluminumhydrideHCID 53843981(R)-ethyl 3-(N-benzyloxycarbonylpyrrolidin-2-yl)-2-propenoate

생성물 1

HCID 54485243(R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3-hydroxypropene수율 52.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred solution of (R)-ethyl 3-(N-benzyloxycarbonylpyrrolidin-2-yl)-2-propenoate (574 g) in tetrahydrofuran (5.7 L) at about -78° C. was added boron trifluoride etherate (295.4 g) and then diisobutylaluminum hydride (1.5M in toluene, 3.91 L, 3.1 eq) added (over two hours) maintaining the temperature below -62° C. The resulting solution was stirred (between -78° and -62° C.) for three hours and then quenched into aqueous citric acid solution (2 kg citric acid in 5 L water plus 4 L ice) over about 40 minutes. The phases were separated and the aqueous phase extracted with ethyl acetate (2×2.1 L). The combined organic solution was dried (over magnesium sulphate) and evaporated, then the residual oil purified by chromatography through silica gel, eluting with mixed ethyl acetate/hexane (9:1 to 4:1) to give the title compound as an oil (260 g), as produced in Example 12A (as an alternative, the residual oil can be purified by chromatography through silica gel eluting with ethyl acetate:hexane (1:1)).

후처리

  1. temperaturemaintaining the temperature below -62° C
  2. customquenched into aqueous citric acid solution (2 kg citric acid in 5 L water plus 4 L ice) over about 40 minutes
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted with ethyl acetate (2×2.1 L)
  5. dry with materialThe combined organic solution was dried (over magnesium sulphate)
  6. customevaporated
  7. customthe residual oil purified by chromatography through silica gel
  8. washeluting with mixed ethyl acetate/hexane (9:1 to 4:1)

출처 및 근거

ORD 기록
ord-864d11da6cd942458c7b2d4a00441500
출처 데이터셋
uspto-grants-1996_09
특허 번호
US05559129

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