HCID 13502055, compound → HCID 70481594, compound

HRID 1981288Notes

Reaction equation

HRID 1981288 reaction equation
C([O:3][C:4](=[O:23])[C@H:5]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][CH3:8])C.[H][H]>O1CCCC1.[Rh]>[C:12]([O:11][C:9]([N:6]([CH2:7][CH3:8])[C@H:5]([C:4]([OH:23])=[O:3])[CH2:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:10])([CH3:14])([CH3:15])[CH3:13]

Participants

5

Reactant 2

HCID 13502055HCID 13502055, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 70481594HCID 70481594, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 8028TetrahydrofuranSolvent

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. customwas catalytically hydrogenated at 80°
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated to an oil which
  4. customcrystallized

Sources & evidence

ORD record
ord-9c57388960b94a28b1bd0f304cb6e9ac
Source dataset
uspto-grants-1985_04
Patent number
US04514332

Reaction notes

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