Potassium Iodide → HCID 71254893, compound

Temperature

100 °C

A sealed tube containing a suspension of Intermediate 39A (0.500 g, 2.340 mmol), potassium carbonate (0.485 g, 3.51 mmol), potassium iodide (0.039 g, 0.234 mmol), and tert-butyl bromoacetate (0.415 ml, 2.81 mmol) in DMA (4.68 mL) was warmed to 100° C. After 3 h, additional tert-butyl bromoacetate (0.415 mL, 2.81 mmol) was added and the reaction was heated at 100° C. After 22 h, the reaction was stopped and cooled to rt. The reaction was filtered, eluting with diethyl ether. The filtrate was partitioned between diethyl ether and water and the layers were separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to give a clear, yellow liquid weighing 1.35 g. Purification by normal phase chromatography gave 1.2:1 mixture of Intermediate 39A and methyl 2-(2-(tert-butoxy)-2-oxoethyl)(3-chlorophenyl)amino)propanoate (0.375 g) as a clear, colorless viscous oil. MS (ESI) m/z: 350.0 (M+Na)+. A clear, colorless solution of Intermediate 39A and methyl 2-((2-(tert-butoxy)-2-oxoethyl)(3-chlorophenyl)amino)propanoate (0.375 g, 1.144 mmol) in 50% TFA/DCM (16.34 mL) was stirred at rt. After 3 h, the reaction was concentrated to give a pink oil. The oil was partitioned between EtOAc and 0.5 M NaOH and the layers were separated. The organic layer was extracted with 0.5 M NaOH (2×). The combined aqueous layers were extracted with EtOAc, acidified with 1.0 N HCl to give a cloudy mixture, and then extracted with EtOAc (3×). The organic layers following acidification were combined, washed with brine, dried over sodium sulfate, filtered and concentrated to give the desired product (0.130 g) as a clear, yellow residue. MS (ESI) m/z: 272.0 (M+H)+.

1. additionA sealed tube containing
2. temperaturethe reaction was heated at 100° C
3. waitAfter 22 h
4. temperaturecooled to rt
5. filtrationThe reaction was filtered
6. washeluting with diethyl ether
7. customThe filtrate was partitioned between diethyl ether and water
8. customthe layers were separated
9. extractionThe aqueous layer was extracted with diethyl ether
10. washThe combined organic layers were washed with brine
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customto give a clear, yellow liquid
15. customPurification by normal phase chromatography
16. customgave
17. waitAfter 3 h
18. concentrationthe reaction was concentrated
19. customto give a pink oil
20. customThe oil was partitioned between EtOAc and 0.5 M NaOH
21. customthe layers were separated
22. extractionThe organic layer was extracted with 0.5 M NaOH (2×)
23. extractionThe combined aqueous layers were extracted with EtOAc
24. customto give a cloudy mixture
25. extractionextracted with EtOAc (3×)
26. washwashed with brine
27. dry with materialdried over sodium sulfate
28. filtrationfiltered
29. concentrationconcentrated

ORD record

ord-6e4716af2d03471bb0544eeb8f731913

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901115B2