Triethylamine → 4-Chloro-2-(3-methoxycarbonyl-2(R)-methyl-propionylamino)-benzoic acid methyl ester

Temperature

22 °C

(R)-(+)-2-Methylsuccinic acid 4-methyl ester (1 g, 6.8 mmol) was dissolved in CH2Cl2 (40 mL). Oxalyl chloride [2M in CH2Cl2 (3.7 mL, 7.4 mmol)] was then added followed by a few drops of DMF (0.1 mL). The mixture was stirred at 22° C. for 3 h, after which it was concentrated under reduced pressure. The resulting residue was then suspended in CH2Cl2 (10 mL) and added slowly to a stirring solution of methyl 2-amino-4-chlorobenzoate (i-i) (1.26 g, 6.8 mmol) in triethylamine (3.76 mL, 27.2 mmol) in CH2Cl2 (40 mL). The reaction mixture was allowed to stir at 22° C. for 1 h. The mixture was then partitioned between CH2Cl2 (50 mL) and H2O (50 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL) and the combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to dryness. The resulting orange residue was purified by column chromatography, eluting with 20% ethyl acetate in hexane to give ii-i as a clear oil (1.8 g, 85% yield): MS m/z═314 (M+H).

1. concentrationafter which it was concentrated under reduced pressure
2. stirringto stir at 22° C. for 1 h
3. customThe mixture was then partitioned between CH2Cl2 (50 mL) and H2O (50 mL)
4. extractionThe aqueous layer was extracted with CH2Cl2 (3×50 mL)
5. washthe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness
9. customThe resulting orange residue was purified by column chromatography
10. washeluting with 20% ethyl acetate in hexane

ORD record

ord-5d344a57c2274f18933f152e9b1abcae

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07459448B2