Sodium Carbonate → Cbz-4-nitrophenylalanine

HRID 2388643Notes

Reaction equation

HRID 2388643 reaction equation
[OH-].[Na+].[N+:3]([C:6]1[CH:17]=[CH:16][C:9]([CH2:10][C@@H:11]([C:13]([OH:15])=[O:14])[NH2:12])=[CH:8][CH:7]=1)([O-:5])=[O:4].C(=O)([O-])[O-].[Na+].[Na+].Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>O>[C:25]([NH:12][C@H:11]([C:13]([OH:15])=[O:14])[CH2:10][C:9]1[CH:8]=[CH:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:17][CH:16]=1)([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 137064-Nitro-3-phenyl-L-alanineHCID 14798Sodium Hydroxide

Product 1

HCID 12086111Cbz-4-nitrophenylalanineYield 99.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium hydroxide (10 g, 0.25 m) is dissolved in water (300 ml). To this solution 4-nitrophenylalanine (50.3 g, 0.22 m) is added and stirred until complete dissolution. To the resulting solution the sodium carbonate (28.8 g, 0.26 m) is added and stirred suspension is cooled in an ice bath to +8° C. Benzyl chloroformate (44.7 g, 0.26 m) is added dropwise with vigorous stirring, maintaining internal temperature in +6° to +9° C. range. The mixture is stirred at +6° C. for additional 1 hr, transferred to the separatory funnel and washed with ether (2×150 ml). Aqueous phase is placed in a large Erlenmeyer flask (2L) and is cautiously acidified with dil. aq. HCl to pH=2 and extracted with ethyl acetate (4×500 ml). The combined extracts are washed with water and dried with MgSO4. The solution is filtered and filtrate evaporated, residue is dissolved in ethyl acetate (150 ml) and diluted with hexane (500 ml). Crystalline material is filtered off and rinsed with cold solvent, air dried to give Cbz-4-nitrophenylalanine, 75 g (99.5% yield).

Workup

  1. stirringstirred suspension
  2. temperatureis cooled in an ice bath to +8° C
  3. temperaturemaintaining internal temperature in +6° to +9° C. range
  4. stirringThe mixture is stirred at +6° C. for additional 1 hr
  5. washwashed with ether (2×150 ml)
  6. customAqueous phase is placed in a large Erlenmeyer flask
  7. extractionextracted with ethyl acetate (4×500 ml)
  8. washThe combined extracts are washed with water
  9. dry with materialdried with MgSO4
  10. filtrationThe solution is filtered
  11. customfiltrate evaporated
  12. dissolutionresidue is dissolved in ethyl acetate (150 ml)
  13. additiondiluted with hexane (500 ml)
  14. filtrationCrystalline material is filtered off
  15. washrinsed with cold solvent, air
  16. customdried

Sources & evidence

ORD record
ord-d435e4f8435744bc83a97b862960e193
Source dataset
uspto-grants-2012_09
Patent number
US08269009B2

Reaction notes

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