Sulfuric Acid → N-(benzyloxycarbonyl)-4-iodo-3-methyl-L-phenylalanine methyl ester

HRID 844874Notes

Reaction equation

HRID 844874 reaction equation
S(=O)(=O)(O)O.Cl.[CH3:7][O:8][C:9](=[O:31])[C@H:10]([CH2:22][C:23]1[CH:28]=[CH:27][C:26](N)=[C:25]([CH3:30])[CH:24]=1)[NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].N([O-])=O.[Na+].[I-:36].[K+]>O>[CH3:7][O:8][C:9](=[O:31])[C@H:10]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([I:36])=[C:25]([CH3:30])[CH:24]=1)[NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 69336581n-(Benzyloxycarbonyl)-4-amino-3-methyl-l-phenylalanine methyl ester hydrochloride salt

Product 1

HCID 69336706N-(benzyloxycarbonyl)-4-iodo-3-methyl-L-phenylalanine methyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent4×

Conditions

Temperature
-1 °C

Procedure

A suspension of sulfuric acid (0.3 mL), water (36 mL) and N-(benzyloxycarbonyl)-4-amino-3-methyl-L-phenylalanine methyl ester hydrochloride salt (2.9 mmol, 1.1 g) was heated to obtain a clear solution. Then, it was cooled to −1° C. (ice-bath) and a solution of sodium nitrite (5.8 mmol, 400 mg) in water (8 mL) was added dropwise. The reaction mixture was stirred for 30 min, and a solution of potassium iodide (8.7 mmol, 1.5 g) in water (6 mL) was added to obtain a brown suspension. After stirring for 30 min, the reaction mixture was allowed to warm to room temperature and was stirred for 1 h. Then, the reaction mixture was diluted with water (100 mL) and was extracted with ethyl acetate (3×50 mL). The combined extracts were washed with saturated sodium bisulfite solution (100 mL) and brine solution (100 mL) and were dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration gave a crude product, which was purified by silica gel chromatography using a Biotage (40m) column to afford 0.84 g (64% yield) of N-(benzyloxycarbonyl)-4-iodo-3-methyl-L-phenylalanine methyl ester as an amorphous white solid. ES-HRMS m/e calcd for C19H20INO4 (M+Na) 476.0329, found 476.0336.

Workup

  1. temperaturewas heated
  2. customto obtain a clear solution
  3. customto obtain a brown suspension
  4. stirringAfter stirring for 30 min
  5. temperatureto warm to room temperature
  6. stirringwas stirred for 1 h
  7. extractionwas extracted with ethyl acetate (3×50 mL)
  8. washThe combined extracts were washed with saturated sodium bisulfite solution (100 mL) and brine solution (100 mL)
  9. dry with materialwere dried over anhydrous magnesium sulfate
  10. filtrationFiltration of the drying agent and concentration
  11. customgave a crude product, which
  12. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-1ba49bb172ec47318957736e1ff5ba73
Source dataset
uspto-grants-2002_04
Patent number
US06380387B1

Reaction notes

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