Formic Acid → methyl (Z)-(2S,3S,4R)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate

HRID 1492016Notes

Reaction equation

HRID 1492016 reaction equation
[OH:1][C@@H:2]1[CH2:6][O:5][C@H:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[C@H:3]1[CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)=O.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[OH:1][C@H:2]1[CH2:6][O:5][C@H:4]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[C@H:3]1[CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 86748312methyl (Z)-(2S,3S,4S)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate

Product 1

HCID 86748313methyl (Z)-(2S,3S,4R)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoateYield 97.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 12.97 g (0.0425 mol) of methyl (Z)-(2S,3S,4S)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate, 26.57 g (0.101 mol) of triphenylphosphine and 3.32 g (2.72 mL, 0.069 mol) of 95% formic acid in 130 ml of tetrahydrofurane is added dropwise with stirring under argon at 10° C. 17.63 g (15.94 ml, 0.101 mol) of diethyl azodicarboxylate over a period of 10 min. The mixture is stirred at room temperature for one h and evaporated. The residue is triturated with ether and the mixture is allowed to stand at 0° C. overnight. The precipitated triphenylphosphine oxide is filtered and washed with ether. The combined filtrates and washings axe evaporated to dryness. The residue is dissolved in 130 ml of methanol and hydrogen chloride gas is bubbled through the solution for 3 to 5 min. The mixture is stirred for 30 min and evaporated to dryness. The residue is dissolved in 56 ml of water and the solution is extracted with ethyl acetate (3×). The aqueous layer is mixed with 100 ml of methylene chloride and neutralized with solid sodium bicarbonate with vigorous stirring. The layers are separated and the aqueous layer is extracted with methylene chloride (3×). The combined methylene chloride extracts are washed with brine, dried (MgSO4) and evaporated to give 12.68 g of methyl (Z)-(2S,3S,4R)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate as oil with elemental analysis: C,66.1; H,7.36; N,4.89 (theory: C,66.86; H,7.59; N,4.59) and mass spectrum m/z 306 (M+1) (Calcd. MW=305.38).

Workup

  1. stirringThe mixture is stirred at room temperature for one h
  2. customevaporated
  3. customThe residue is triturated with ether
  4. filtrationThe precipitated triphenylphosphine oxide is filtered
  5. washwashed with ether
  6. customThe combined filtrates and washings axe evaporated to dryness
  7. dissolutionThe residue is dissolved in 130 ml of methanol
  8. customhydrogen chloride gas is bubbled through the solution for 3 to 5 min
  9. stirringThe mixture is stirred for 30 min
  10. customevaporated to dryness
  11. dissolutionThe residue is dissolved in 56 ml of water
  12. extractionthe solution is extracted with ethyl acetate (3×)
  13. additionThe aqueous layer is mixed with 100 ml of methylene chloride and neutralized with solid sodium bicarbonate with vigorous stirring
  14. customThe layers are separated
  15. extractionthe aqueous layer is extracted with methylene chloride (3×)
  16. washThe combined methylene chloride extracts are washed with brine
  17. dry with materialdried (MgSO4)
  18. customevaporated

Sources & evidence

ORD record
ord-b89eae1af0c34d57ab820e86757a3ef3
Source dataset
uspto-grants-1994_12
Patent number
US05371096

Reaction notes

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