Water → Methyl 2-amino-3-fluorobenzoate

HATU (230.1 mg, 0.605 mmol) was added to a solution of 5-methoxy-2-(methylsulfonamido)benzoic acid (intermediate 9) (129.2 mg, 0.527 mmol) in 4 mL of anhydrous DMF at room temperature. After 15 min of stirring, intermediate 6 (128.4 mg, 0.403 mmol) was added followed immediately by triethylamine (0.20 mL, 1.43 mmol). Reaction mixture stirred at room temperature for 18 hours under argon. Mixture was then poured into 40 mL of H2O and extracted three times with 40 mL of ethyl acetate. The combined organic layers were washed with 80 mL Brine, dried (MgSO4), filtered, and concentrated under reduced pressure leaving a residue. Product was purified by silica gel column chromatography (0-10% Methanol in Dichloromethane) and then prep HPLC (15-100% Acetonitrile (with 0.1% trifluoroacetic acid) in water (with 0.1% trifluoroacetic acid)) to yield compound 10 (56 mg, 30%) as a white solid, trifluoroacetate salt, after lyophilization.

1. customReaction mixture
2. stirringstirred at room temperature for 18 hours under argon
3. extractionextracted three times with 40 mL of ethyl acetate
4. washThe combined organic layers were washed with 80 mL Brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customleaving a residue
9. customProduct was purified by silica gel column chromatography (0-10% Methanol in Dichloromethane)

ORD record

ord-7510f617de5348d493bcb12554f87d98

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238039B2