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

HRID 1077870Notes

Reaction equation

HRID 1077870 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-7e995ed38490476f9c7bfcb5ba45b35a
Source dataset
uspto-grants-1996_08
Patent number
US05545644

Reaction notes

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