Ethyl Acetate → benzyl (2S,4R)-2-(4-methyl-1-pentenyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidinecarboxylate

HRID 2249676Notes

Reaction equation

HRID 2249676 reaction equation
[I-].[CH2:2]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:3][CH:4]([CH3:6])[CH3:5].C([Li])CCC.[CH:31]([C@@H:33]1[CH2:37][C@@H:36]([O:38][CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[CH2:35][N:34]1[C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])=O.C(OCC)(=O)C>O1CCCC1.CCCCCC.O>[CH3:5][CH:4]([CH3:6])[CH2:3][CH:2]=[CH:31][C@@H:33]1[CH2:37][C@@H:36]([O:38][CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[CH2:35][N:34]1[C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 22245250(3-Methylbutyl)(triphenyl)phosphanium iodideHCID 86630052HCID 86630052, compoundHCID 178418339Butyllithium

Product 1

HCID 86630053benzyl (2S,4R)-2-(4-methyl-1-pentenyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidinecarboxylateYield 48.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

In 11 ml of tetrahydrofuran is suspended 3.34 g of isopentyltriphenylphosphonium iodide, to which is dropwise added 4.3 ml of a 1.53 mol/L solution of n-butyllithium in n-hexane at −25° C. to −20° C. After stirring the mixture at −25° C. to −15° C. for one hour, the temperature is elevated to ambient temperature in one hour. To the reaction mixture is dropwise added 1.10 g of benzyl (2S,4R)-2-formyl-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidinecarboxylate dissolved in 11 ml of tetrahydrofuran over a period of 20 minutes. The mixture thus obtained is stirred at ambient temperature for 5 hours. The reaction mixture is added to a mixture of ethyl acetate and water, and the organic layer is separated. The organic layer thus obtained is washed with water and saturated aqueous solution of sodium chloride successively and dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue thus obtained is purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=4:1) to obtain 0.62 g of benzyl (2S,4R)-2-(4-methyl-1-pentenyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidinecarboxylate as a light yellow oily product.

Workup

  1. customat −25° C. to −20° C
  2. waitthe temperature is elevated to ambient temperature in one hour
  3. customThe mixture thus obtained
  4. stirringis stirred at ambient temperature for 5 hours
  5. customthe organic layer is separated
  6. customThe organic layer thus obtained
  7. washis washed with water and saturated aqueous solution of sodium chloride successively
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationthe solvent is distilled off under reduced pressure
  10. customThe residue thus obtained
  11. customis purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-f78c99c5f963468cb165680a4e7a34bf
Source dataset
uspto-grants-2008_01
Patent number
US07314888B1

Reaction notes

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