Sodium Carbonate → Cbz-4-nitrophenylalanine

HRID 1271223Notes

Reaction equation

HRID 1271223 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-nitrophenylalanine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium hydroxide (10 g, 0.25 mol) was dissolved in water (300 mL). To this solution the 4-nitrophenylalanine (50.3 g, 0.22 mol) was added and stirred until complete dissolution. To the resulting solution the sodium carbonate (28.8 g, 0.26 mol) was added and stirred suspension was cooled in an ice bath to +8° C. The benzyl chloroformate (44.7 g, 0.26 mol) was added drop wise with vigorous stirring, maintaining internal temperature in +6° to +9° C. range. The mixture was stirred at +6° C. for additional 1 hr, transferred to the separatory funnel and washed with ether (2×150 mL). Aqueous phase was placed in a large Erlenmeyer flask (2 L) and was cautiously acidified with dil. aq. HCl to pH=2 and extracted with ethyl acetate (4×500 mL). The combined extracts were washed with water and dried with MgSO4. The solution was filtered and filtrate evaporated, residue was dissolved in ethyl acetate (150 mL) and diluted with hexane (500 mL). Crystalline material was filtered off and rinsed with cold solvent, air dried to give Cbz-4-nitrophenylalanine, 75 g (99.5% yield) 19D. 1H-NMR, DMSO-d6, (δ): 12.85 (bs, 1H), 8.12 (d, 2H, J=9 Hz), 7.52 (d, 2H, J=9 Hz), 7.30 (m, 5H), 4.95 (s, 2H), 4.28 (m, 1H), 3.32 (bs, 11H), 3.10 (m, 2H). 13C-NMR (δ): 173.1, 156.3, 146.6, 137.3, 130.8, 128.5, 128.0, 127.8, 123.5, 65.6, 55.1, 36.6. MS (m/z): 367.1 [M+23].

Workup

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

Sources & evidence

ORD record
ord-3f56565e29b64c11a87425822ada616a
Source dataset
uspto-grants-2007_04
Patent number
US07205310B2

Reaction notes

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