Methyl p-toluenesulfonate → HCID 86586537, compound

To 2.2 g (5.8 mmole) of toluene-4-sulfonic acid (2R)-8-amino-7-nitro-2,3-dihydro-benzo(1,4)dioxin-2-ylmethyl ester in 100 mL of methylene chloride was added 1.3 g (10 mmole) of N,N-diisopropylethylamine, followed by 2.1 g (10 mmole) of trifluoroacetic anhydride. The mixture was stirred at room temperature for 2 hours, then washed with 100 mL portions of 2 N HCl (aq) and water, dried over sodium sulfate, filtered through silica gel, using additional methylene chloride to fully elute the product, and concentrated in vacuum to 2.6 g (5.4 mmole) of the trifluoroacetamide. This was dissolved in 50 mL of N,N-dimethylformamide and 1.2 g (6.5 mmole) of methyl tosylate and 3.0 g (22 mmole) of potassium carbonate added. The mixture was heated at 50-60° C. under nitrogen for 15 hours. After the mixture had cooled, it was diluted to 300 mL with ethyl acetate and washed with 300 mL of water. The aqueous phase was back-extracted with 200 mL of ethyl acetate and the combined organics were washed with 250 mL portions of water and saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was dissolved in 300 mL of methanol and 5.0 g (36 mmole) of potassium carbonate added. This mixture was stirred at room temperature for 24 hours, then filtered and concentrated in vacuum. The residue was column chromatographed on silica gel with methylene chloride as eluant to give 0.80 g of the (R)-enantiomer of the title compound as a yellow solid, m.p. 149-151° C.

1. washwashed with 100 mL portions of 2 N HCl (aq) and water
2. dry with materialdried over sodium sulfate
3. filtrationfiltered through silica gel
4. washto fully elute the product
5. temperatureThe mixture was heated at 50-60° C. under nitrogen for 15 hours
6. temperatureAfter the mixture had cooled
7. washwashed with 300 mL of water
8. extractionThe aqueous phase was back-extracted with 200 mL of ethyl acetate
9. washthe combined organics were washed with 250 mL portions of water and saturated brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuum
13. dissolutionThe residue was dissolved in 300 mL of methanol
14. stirringThis mixture was stirred at room temperature for 24 hours
15. filtrationfiltered
16. concentrationconcentrated in vacuum
17. customchromatographed on silica gel with methylene chloride as eluant

ORD record

ord-8c431c4fc25247f69b55b70859084914

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06573283B2