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

HRID 744155Notes

Reaction equation

HRID 744155 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)).

Workup

  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)

Sources & evidence

ORD record
ord-864d11da6cd942458c7b2d4a00441500
Source dataset
uspto-grants-1996_09
Patent number
US05559129

Reaction notes

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