L-Alanine → N-(tert-Buloxycarbonyl)-3,4-dihydroxy-L-phenylalanine

HRID 1580725Notes

Reaction equation

HRID 1580725 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH2:11][C@@H:12]([C:14]([OH:16])=[O:15])[NH2:13])[CH:7]=[CH:8][C:9]=1[OH:10].N[C@H](C(O)=O)C.B(O)(O)O.[C:27]([O:31][C:32](N=[N+]=[N-])=[O:33])([CH3:30])([CH3:29])[CH3:28]>O>[C:27]([O:31][C:32]([NH:13][C@H:12]([C:14]([OH:16])=[O:15])[CH2:11][C:6]1[CH:7]=[CH:8][C:9]([OH:10])=[C:4]([OH:3])[CH:5]=1)=[O:33])([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 5

HCID 5950L-AlanineHCID 6047LevodopaHCID 7628Boric AcidHCID 14798Sodium Hydroxide3×HCID 61256Carbonazidic acid, 1,1-dimethylethyl ester2×

Product 1

HCID 14217229N-(tert-Buloxycarbonyl)-3,4-dihydroxy-L-phenylalanine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-N aqueous sodium hydroxide is added in an argon atmosphere to a mixture of 100 g of 3-(3,4-dihydroxyphenyl)-L-alanine, 200 g of borax and 1000 ml of water, up to pH 9.5 (pH meter). A boric acid complex forms, in which the hydroxyl groups on the phenyl ring of the alanine derivative are esterified with boric acid. Half of the crude tertbutoxycarbonyl azide prepared from 120 g of tertbutoxycarbonyl hydrazide is then added in one portion, and the mixture is stirred at room temperature for 6 hours, the pH being held between 9.3 and 9.8 by the occasional addition of 2-N aqueous sodium hydroxide. The remaining tertbutoxycarbonyl azide is subsequently added and the mixture is stirred for a further 14 hours. After 14 hours, the pH falls to 8.5. It is then brought to pH 9.5 with 2-N aqueous sodium hydroxide, and the mixture is stirred for a further 2 hours. The mixture is then extracted twice with 300 ml of diethyl ether each time. The aqueous phase is brought to pH 2.5 with 10% aqueous citric acid solution, saturated with sodium chloride, and extracted twice with 300 ml of ethyl acetate each time. The combined organic extracts are washed 10 times with 500 ml of water each time, dried over sodium sulphate and then concentrated under vacuum. The glassy residue crystallizes on digesting with cyclohexane. After two recrystallizations from ethyl acetate/cyclohexane, there is obtained 100 g of N-(tertbutoxycarbonyl)-3-(3,4-dihydroxyphenyl)-L-alanine of melting point 148°C.; [α]D25 = +16.4° (c = 1%, methanol)

Workup

  1. additionis then added in one portion
  2. stirringthe mixture is stirred for a further 14 hours
  3. waitAfter 14 hours
  4. stirringthe mixture is stirred for a further 2 hours
  5. extractionThe mixture is then extracted twice with 300 ml of diethyl ether each time
  6. extractionextracted twice with 300 ml of ethyl acetate each time
  7. washThe combined organic extracts are washed 10 times with 500 ml of water each time
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated under vacuum
  10. customThe glassy residue crystallizes
  11. customAfter two recrystallizations from ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-9fdd79d9eb3d4f938329522ee0658cf2
Source dataset
uspto-grants-1976_01
Patent number
US03933859

Reaction notes

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