Tetrahydrofuran → HCID 13502055, compound

HRID 1981287Notes

Reaction equation

HRID 1981287 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O1CC[CH2:22][CH2:21]1.[C:25]([Li])(C)(C)[CH3:26].F[B-](F)(F)F.C([O+](CC)CC)C>O>[CH2:21]([O:11][C:10](=[O:12])[C@H:2]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[N:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:25][CH3:26])[CH3:22]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 2723982Triethyloxonium tetrafluoroborateHCID 178418306HCID 178418306, compound

Product 1

HCID 13502055HCID 13502055, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 2.65 g (10 mmole) of Boc-Phe in 50 ml of cold (ca. -78°), dry tetrahydrofuran was added 12 ml (ca. 22 mmole) of 1.9M t-butyllithium. After thirty minutes, the mixture was allowed to warm to -20° and then to react with 4.2 g (22 mmole) of triethyloxonium tetrafluoroborate. After thirty minutes, the mixture was allowed to warm to 0° and was then poured into water and extracted with dichloromethane. The organic extract was washed sequentially with portions of 5% aqueous sodium bicarbonate and water, dried over sodium sulfate, filtered, and concentrated to dryness. Distillation (ca. 130°-200°) afforded an oil that was further purified by column chromatography on silica gel to give t-butoxycarbonyl-N-ethylphenylalanine ethyl ester. To a stirred mixture of this ester intermediate in tetrahydrofuran was added a two-fold (molar) quantity of potassium hydroxide in water. After the mixture was stirred overnight, an equal volume of dichloromethane was added and acidified to pH 3 with 0.5M sodium bisulfate. The aqueous layer was separated and washed with dichloromethane, and all organic layers were recombined. This organic solution was further washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo to dryness. Column chromatography on silica gel afforded de-esterified t-butoxycarbonyl-N-ethylphenylalanine. A solution of 2.6 g of this protected amino acid intermediate in about 100 ml of tetrahydrofuran was catalytically hydrogenated at 80° using 60 psi hydrogen gas and 5% rhodium on carbon. The mixture was filtered and the filtrate was concentrated to an oil which crystallized on standing to afford 2.0 g of the title compound. The title compound was used in subsequent reactions without further purification.

Workup

  1. waitAfter thirty minutes
  2. temperatureto warm to -20°
  3. waitAfter thirty minutes
  4. temperatureto warm to 0°
  5. extractionextracted with dichloromethane
  6. extractionThe organic extract
  7. washwas washed sequentially with portions of 5% aqueous sodium bicarbonate and water
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. distillationDistillation (ca. 130°-200°)
  12. customafforded an oil that
  13. customwas further purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-63b6db6162294ec98cd6915889671abc
Source dataset
uspto-grants-1985_04
Patent number
US04514332

Reaction notes

Loading…