Lithium Hydroxide → HCID 58449392, compound

To a stirred solution of methyl 5-amino-4′-methylbiphenyl-3-carboxylate (410 mg, 1.7 mmol) in CH2Cl2 (30 mL) and N,N-diisopropylethylamine (0.44 mL, 2.5 mmol) at 0° C. was added 5-bromopentanoyl chloride (370 mg, 1.9 mmol). The mixture was stirred at room temperature overnight and then washed with aq. Na2CO3 solution and brine, dried (Na2SO4), and concentrated. The residue was dissolved in THF (30 mL) and cooled to 0° C. Sodium tert-butoxide (200 mg, 2.0 mmol) was added and the mixture was stirred at room temperature for 3 h. LC-MS indicated the cyclization reaction was complete. MeOH (20 mL) and water (10 mL) were added followed by lithium hydroxide (120 mg, 5.1 mmol). The mixture was stirred at room temperature for another 3 h, and LC-MS indicated the saponification was complete. The mixture was concentrated in vacuo. The residue was treated with water and acidified to pH 2-3 with 1N HCl, extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to afford a white solid. LC-MS: 310.1 [M+1]+.

1. washwashed with aq. Na2CO3 solution and brine
2. dry with materialdried (Na2SO4)
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in THF (30 mL)
5. temperaturecooled to 0° C
6. stirringthe mixture was stirred at room temperature for 3 h
7. customthe cyclization reaction
8. stirringThe mixture was stirred at room temperature for another 3 h
9. concentrationThe mixture was concentrated in vacuo
10. additionThe residue was treated with water
11. extractionextracted with EtOAc (3×50 mL)
12. washThe combined organic layers were washed with brine
13. dry with materialdried (Na2SO4)
14. concentrationconcentrated
15. customto afford a white solid

ORD record

ord-5290aafd5da54a7895bfb2f6ac765771

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133122B2