Sulfuric Acid → 4-Nitro-3-phenyl-L-alanine

HRID 2388644Notes

Reaction equation

HRID 2388644 reaction equation
C([NH:11][C@H:12]([C:23]([OH:25])=[O:24])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)(OCC1C=CC=CC=1)=O.CC(=C)C.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(=O)=O.C(OCC)(=O)C>[N+:20]([C:17]1[CH:16]=[CH:15][C:14]([CH2:13][C@@H:12]([C:23]([OH:25])=[O:24])[NH2:11])=[CH:19][CH:18]=1)([O-:22])=[O:21]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 8255IsobutyleneHCID 10340Sodium CarbonateHCID 12086111Cbz-4-nitrophenylalanine

Product 1

HCID 137064-Nitro-3-phenyl-L-alanine

Reagents, catalysts & solvents 3

HCID 280Carbon DioxideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

The Cbz-4-nitrophenylalanine (75 g, 0.22 m) is dissolved in dioxane (300 ml). The resulted stirred solution is cooled in Dry Ice bath to −20° C. (internal). The liquefied isobutylene (approx. 290 ml) is added followed by conc. sulfuric acid (35 ml) added in three equal portions, 30 min apart. The addition of acid is a very exothermic process, accompanied by substantial degree of polymerization. Efficient mechanical stirring is essential at this stage. Resulted mixture is stirred for 20 hr, allowing to warm up to ambient temperature then is cautiously poured into sat. aq. sodium carbonate solution (2L) and diluted with ethyl acetate (600 ml). Organic layer is separated and aqueous layer is extracted with ethyl acetate (2×200 ml). Combined extracts are washed with water and dried with sodium sulfate. The solution is filtered and evaporated to dryness. The residue is taken up in ethyl acetate/hexane mixture (500 ml; 1:1) and filtered through plug of silica gel (ca. 2×2 in). The silica is rinsed with an additional amount of the same solvent (2 L total) and the filtrates are evaporated to give fully protected 4-nitrophenylalanine as a viscous oil, 73 g (83% after two steps).

Workup

  1. additionadded in three equal portions, 30 min apart
  2. additionThe addition of acid
  3. customaccompanied by substantial degree of polymerization
  4. stirringEfficient mechanical stirring
  5. customResulted mixture
  6. stirringis stirred for 20 hr
  7. customOrganic layer is separated
  8. extractionaqueous layer is extracted with ethyl acetate (2×200 ml)
  9. washCombined extracts are washed with water
  10. dry with materialdried with sodium sulfate
  11. filtrationThe solution is filtered
  12. customevaporated to dryness
  13. filtrationfiltered through plug of silica gel (ca. 2×2 in)
  14. washThe silica is rinsed with an additional amount of the same solvent (2 L total)
  15. customthe filtrates are evaporated

Sources & evidence

ORD record
ord-3e2c66f0482b4052815b02c4845cd905
Source dataset
uspto-grants-2012_09
Patent number
US08269009B2

Reaction notes

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