Sodium Carbonate → Cbz-4-nitrophenylalanine

Participants

Reaction Steps

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].

Provenance & Evidence