L-Phenylalanine → Benzyloxycarbonyl-L-phenylalanine

HRID 1680563Notes

Reaction equation

HRID 1680563 reaction equation
[OH-].[Na+].[NH2:3][C@H:4]([C:12]([OH:14])=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:15](Cl)([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16]>>[C:15]([NH:3][C@H:4]([C:12]([OH:14])=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16]

Participants

4

Reactant 3

HCID 6140L-PhenylalanineHCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide2×

Product 1

HCID 70878Benzyloxycarbonyl-L-phenylalanine

Procedure

To 30 ml of a 1 N sodium hydroxide solution is added 4.95 g of L-phenylalanine. The solution is cooled and stirred in an ice bath and 5.4 ml of a 6.1 M solution of carbobenzoxychloride is added dropwise along with additional 1 N sodium hydroxide solution so that the pH remains at 11.0-11.5. The reaction mixture is washed with ether. The aqueous layer is acidified to pH 1.0 with 12 N hydrochloric acid, then the solution is extracted with ethyl acetate. The ethyl acetate extract is separated and is washed three times with water then dried over magnesium sulfate. The solvent is removed under vacuum. The residue crystallizes on rubbing with water to give N-carbobenzoxy-L-phenylalanine. 3.99 Grams of methyl 3-amino-1-adamantanecarboxylate hydrochloride and 4.78 g of carbobenzoxy-L-phenylalanine are dissolved in 40 ml methylene chloride. To this solution is added 1.8 ml of N-methylmorpholine followed immediately by 2.19 g of dicyclohexylcarbodiimide. The reaction mixture is allowed to stand for 24 hours at room temperature, then the treatment with carbobenzoxy-L-phenylalanine and dicyclohexylcarbodiimide is repeated. The reaction mixture is again allowed to stand for 24 hours at room temperature. The dicyclohexylurea is removed by filtration and washed with methylene chloride. The combined filtrates are washed twice with 0.5 M potassium bisulfate, water and 1 M solution of potassium bicarbonate and dried over magnesium sulfate. The dicloromethane is removed under vacuum and the residue is purified by low pressure chromatography on silica gel using mixtures of hexane and chloroform as eluting solvent to give methyl carbobenzoxy-L-phenylalanyl-3-amino-1-adamantanecarboxylate which has the following structural formula ##STR13## wherein Cbz represents carbobenzoxy.

Workup

  1. temperatureThe solution is cooled
  2. washThe reaction mixture is washed with ether
  3. extractionthe solution is extracted with ethyl acetate
  4. extractionThe ethyl acetate extract
  5. customis separated
  6. washis washed three times with water
  7. dry with materialthen dried over magnesium sulfate
  8. customThe solvent is removed under vacuum
  9. customThe residue crystallizes

Sources & evidence

ORD record
ord-193bf83858a74dbb89890d879134f2c3
Source dataset
uspto-grants-1981_06
Patent number
US04273704

Reaction notes

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