Methanol → HCID 12044228, compound

Temperature

55 °C

To a mixture of N-[(2-chloro-6-methylphenyl)thioxomethyl]-4-nitro-L-phenylalanine methyl ester (3.86 mmol, 1.52 g), zinc dust (˜325 mesh, 39.0 mmol, 2.55 g, 10 equiv.) and ammonium chloride (58.0 mmol, 3.09 g, 15 equiv.) was added methanol (50 mL) and water (25 mL) at room temperature. After addition of water, an exothermic reaction ensued and the temperature rose to between 45 and 50° C. After the suspension was stirred for 2 h at a bath temperature of 50-60° C., TLC analysis of the mixture indicated the absence of starting material. The reaction mixture was filtered through a pad of celite and the filter cake was washed with methanol (50 mL) and water (40 mL). The filtrate was concentrated under vacuum to remove methanol and the product was extracted into ethyl acetate (2×50 mL). The combined extracts were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give 1.3 g (92%) of 4-amino-N-[(2-chloro-6-methylphenyl)thioxomethyl]-L-phenylalanine methyl ester as an amorphous yellow solid, which was used directly for next step. HRMS: Obs. mass, 363.0932. Calcd. mass, 363.0934 (M+H).

1. customan exothermic reaction
2. customrose to between 45 and 50° C
3. filtrationThe reaction mixture was filtered through a pad of celite
4. washthe filter cake was washed with methanol (50 mL) and water (40 mL)
5. concentrationThe filtrate was concentrated under vacuum
6. customto remove methanol
7. extractionthe product was extracted into ethyl acetate (2×50 mL)
8. washThe combined extracts were washed with brine (50 mL)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-a78c61454914469383647a52200d87fc

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06458844B2