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

HRID 744155ノート

反応式

HRID 744155 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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)).

後処理

  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)

出典と根拠

ORDレコード
ord-864d11da6cd942458c7b2d4a00441500
出典データセット
uspto-grants-1996_09
特許番号
US05559129

反応ノート

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