Phosgene → L-Leucine

HRID 874082Notes

Reaction equation

HRID 874082 reaction equation
O[NH:2][C@H:3]([C:8](N)=[O:9])[CH2:4][CH:5]([CH3:7])[CH3:6].C(Cl)(Cl)=[O:12]>C1COCC1.C1(C)C=CC=CC=1>[NH2:2][C@H:3]([C:8]([OH:9])=[O:12])[CH2:4][CH:5]([CH3:7])[CH3:6]

Participants

5

Reactant 2

HCID 6371PhosgeneHCID 14584860HCID 14584860, compound

Product 1

HCID 6106L-LeucineYield 90%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

HO-Leu-NH2 (10.0 g, 76.2 mmol) was suspended in 150 mL of anhydrous THF and heated to 50° C. Phosgene (20% in toluene) (76.0 mL, 152.4 mmol) was added to the amino acid suspension. The amino acid dissolved over the course of approx. 1 hr, forming a clear solution. The solution was concentrated on the rotovap, transferred to a beaker, and hexane was added to precipitate the product. The white solid was isolated by filtration and dissolved in toluene. The solution was filtered over a bed of Celite to remove any insoluble material. An excess of hexane was added to the filtrate to precipitate the product. The NCA was isolated by filtration and dried in vacuo. 9.0 g (75% yield) of Leu NCA was isolated as a white, crystalline solid. 1H NMR (d6-DMSO) δ 9.13 (1H), 4.44 (1H), 1.74 (1H), 1.55 (2H), 0.90 (6H) ppm.

Workup

  1. customforming a clear solution
  2. concentrationThe solution was concentrated on the rotovap
  3. additionwas added
  4. customto precipitate the product
  5. customThe white solid was isolated by filtration
  6. filtrationThe solution was filtered over a bed of Celite
  7. customto remove any insoluble material
  8. additionAn excess of hexane was added to the filtrate
  9. customto precipitate the product
  10. customThe NCA was isolated by filtration
  11. customdried in vacuo

Sources & evidence

ORD record
ord-82f4d78c3b3c49b3a8f6e22690a2ccdc
Source dataset
uspto-grants-2015_03
Patent number
US08980326B2

Reaction notes

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