Trifluoroacetic anhydride → HCID 22243214, compound

Temperature

0 °C

DBU (2.36 mL, 15.2 mmol) and methyl{[(benzyloxy)carbonyl]amino}(dimethoxyphosphoryl)acetate (5.02 g, 15.2 mmol) are dissolved in CH2Cl2 (75 mL). The resulting solution is added drop-wise to a solution of 4-chlorophthalaldehyde (2.31 g, 13.8 mmol) in CH2Cl2 (100 mL) at 0° C. The reaction is stirred for 1 hour at 0° C. and then for 18 hours at rt. The volatiles are evaporated to yield a yellow oil, which is dissolved in CHCl3 (10 mL). DBU (2.36 mL, 15.2 mmol) and TFAA (2.15 mL, 15.2 mmol) are added. The reaction is stirred under N2 for 3 hours and is quenched with 150 mL of saturated NaHCO3 solution. The organic layer is separated, and the aqueous layer is extracted with 2×150 mL of CHCl3. The combined organic layers are dried (MgSO4), filtered, and concentrated to a yellow oil. This mixture is purified by column chromatography using a step gradient of 25% to 45% EtOAc in hexanes in 5% increments. Product containing fractions are concentrated, dissolved in MeOH and loaded onto a column of AGW-×2 resin (H+ form). The column is rinsed with MeOH, and the product is eluted with a solution of 5% TEA in MeOH. The product is concentrated from MeOH/MeCN several times to yield methyl 6-chloroisoquinoline-3-carboxylate as a white solid in 67% purity by HPLC (0.810 g).

1. waitfor 18 hours at rt
2. customThe volatiles are evaporated
3. customto yield a yellow oil, which
4. stirringThe reaction is stirred under N2 for 3 hours
5. customis quenched with 150 mL of saturated NaHCO3 solution
6. customThe organic layer is separated
7. extractionthe aqueous layer is extracted with 2×150 mL of CHCl3
8. dry with materialThe combined organic layers are dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated to a yellow oil
11. customThis mixture is purified by column chromatography
12. additionProduct containing fractions
13. concentrationare concentrated
14. dissolutiondissolved in MeOH
15. washThe column is rinsed with MeOH
16. washthe product is eluted with a solution of 5% TEA in MeOH
17. concentrationThe product is concentrated from MeOH/MeCN several times

ORD record

ord-6636dae40e104e969fc6dbafebf4411b

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07001900B2