L-Alanine → 3-hydroxy-N-[(phenylmethoxy)carbonyl]- L-Tyrosine

HRID 1580726Notes

Reaction equation

HRID 1580726 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:9][C@@H:10]([C:12]([OH:14])=[O:13])[NH2:11])[CH:5]=[CH:6][C:7]=1[OH:8].[OH-].[Na+].N[C@H](C(O)=O)C.B(O)(O)O.[CH2:27]([O:34][C:35](Cl)=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O>[CH2:27]([O:34][C:35]([NH:11][C@H:10]([C:12]([OH:14])=[O:13])[CH2:9][C:4]1[CH:5]=[CH:6][C:7]([OH:8])=[C:2]([OH:1])[CH:3]=1)=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 5950L-AlanineHCID 6047LevodopaHCID 7628Boric AcidHCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide2×

Product 1

HCID 148528073-hydroxy-N-[(phenylmethoxy)carbonyl]- L-TyrosineYield 97.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

77 g of 3-(3,4-dihydroxyphenyl)-L-alanine is added with stirring in an argon atmosphere to a suspension of 140 g of borax in 700 ml of water. The mixture is stirred for 15 minutes and then brought to pH 9 (pH meter) with 2-N aqueous sodium hydroxide. A boric acid complex forms in which the hydroxyl groups on the phenyl ring of the alanine derivative are esterified with boric acid. 77 g of chloroformic acid benzyl ester is subsequently added in portions of about 4 ml in the course of three hours at a temperature between 0°C. and 10°C., the pH of the mixture being held between 9 and 9.5 by the addition of 2-N sodium hydroxide. After the addition, the mixture is cooled to 0°C. and filtered off from a small amount of undissolved material, and the filtrate is extracted twice with 500 ml of diethyl ether each time. The ether extracts are washed once with 100 ml of water and then discarded. The aqueous alkaline extracts are brought to pH 1 with 6-N aqueous sulphuric acid with ice-cooling and then extracted twice with 1,000 ml of diethyl ether each time. The organic extracts are washed four times with 500 ml of water each time, then combined and, after drying over sodium sulphate and animal charcoal, evaporated under vacuum with the addition of toluene. 125.7 g of crude N-benzyloxycarbonyl-3-(3,4-dihydroxyphenyl)-L-alanine is thus obtained as a weakly violet-colored glass; [α]D25 = +1.5°(c = 1.935%, methanol).

Workup

  1. additionAfter the addition
  2. filtrationfiltered off from a small amount of undissolved material
  3. extractionthe filtrate is extracted twice with 500 ml of diethyl ether each time
  4. washThe ether extracts are washed once with 100 ml of water
  5. temperaturecooling
  6. extractionextracted twice with 1,000 ml of diethyl ether each time
  7. washThe organic extracts are washed four times with 500 ml of water each time
  8. dry with materialafter drying over sodium sulphate and animal charcoal
  9. customevaporated under vacuum with the addition of toluene

Sources & evidence

ORD record
ord-5c231908facf4f849480751b0268796a
Source dataset
uspto-grants-1976_01
Patent number
US03933859

Reaction notes

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