Tetrahydrofuran → ethyl (2E)-3-(5-{[(3R)-1-benzyl-3-pyrrolidinyl](tert-butoxycarbonyl)amino}-2-pyrazinyl)acrylate

HRID 2376152Notes

Reaction equation

HRID 2376152 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH2:11]([N:18]1[CH2:22][CH2:21][C@@H:20]([N:23]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:24]2[N:25]=[CH:26][C:27]([C:30](OC)=O)=[N:28][CH:29]=2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Cl-].[NH4+].[O-:43]S([O-])(=O)=O.[Mg+2].[CH2:49]1[CH2:53][O:52][CH2:51][CH2:50]1>CCCCCC>[CH2:11]([N:18]1[CH2:22][CH2:21][C@@H:20]([N:23]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:24]2[N:25]=[CH:26][C:27](/[CH:30]=[CH:50]/[C:51]([O:52][CH2:53][CH3:49])=[O:43])=[N:28][CH:29]=2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 24083Sulfuric acid magnesium salt (1:1)HCID 25517Ammonium ChlorideHCID 21225700DiisobutylaluminumhydrideHCID 68965042methyl 5-{[(3R)-1-benzyl-3-pyrrolidinyl](tert-butoxycarbonyl)amino}-2-pyrazinecarboxylate

Product 1

HCID 86603754ethyl (2E)-3-(5-{[(3R)-1-benzyl-3-pyrrolidinyl](tert-butoxycarbonyl)amino}-2-pyrazinyl)acrylateYield 53%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

0.94 M solution of diisobutylaluminium hydride in hexane (4.82 ml) was added dropwise to a solution of methyl 5-{[(3R)-1-benzyl-3-pyrrolidinyl](tert-butoxycarbonyl)amino}-2-pyrazinecarboxylate (1.01 g) in THF (20 ml) with stirred below −60° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at −55 to −50° C. for 1 hr. To the reaction mixture was added saturated aqueous ammonium chloride (1.28 ml) at the same temperature, then the mixture was stirred at 25° C. for 40 minutes. THF (14 ml) and MgSO4 (4.36 G) were added to the solution, and the mixture was stirred at 25° C. for 15 minutes. The reaction mixture was filtered, and then to the filtrate was added ETHYL (triphenylphosphoranylidene)acetate (1.07 g), and the mixture was stirred at 25° C. for 16 hr. The reaction mixture was poured into a mixture of AcOEt and 5% aqueous NaCl. The separated organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (51 g) using a mixed solvent of hexane and ethyl acetate (7:2 to 2:1). The fractions containing the objective compound were collected and evaporated under reduced pressure. Title compound (584 mg, 53%) was obtained as slightly yellowish oil.

Workup

  1. stirringthe reaction mixture was stirred at −55 to −50° C. for 1 hr
  2. stirringthe mixture was stirred at 25° C. for 40 minutes
  3. stirringthe mixture was stirred at 25° C. for 15 minutes
  4. filtrationThe reaction mixture was filtered
  5. additionto the filtrate was added ETHYL (triphenylphosphoranylidene)acetate (1.07 g)
  6. stirringthe mixture was stirred at 25° C. for 16 hr
  7. additionThe reaction mixture was poured into a mixture of AcOEt and 5% aqueous NaCl
  8. washThe separated organic layer was washed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated in vacuo
  11. customThe resulting residue was purified by column chromatography on silica gel (51 g)
  12. additionThe fractions containing the objective compound
  13. customwere collected
  14. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-00d3ad5e808a4aaaa8284887e6aac1b4
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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