Methylamine → HCID 118098696, compound

To a solution of 2-chloro-5-nitrobenzaldehyde (5 g, 26.9 mmol) in MeOH (100 mL), was added methylamine (33% in EtOH) (14.82 mL, 29.6 mmol). The mixture was stirred at rt for 1 h, cooled to 0° C. and treated with NaBH4 (1.223 g, 32.3 mmol). The mixture was stirred at rt for 30 min, then was concentrated. The residue was dissolved in THF (50 mL), treated with water (20 mL) and sat. NaHCO3 (20 mL). After stirring for 10 min, Cbz-Cl (4.62 mL, 32.3 mmol) was added dropwise. The mixture was stirred at rt over night. THF was removed under reduced pressure. The mixture was extracted with EtOAc (2×). The organic phase was washed with brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (loaded in chloroform onto a 120 g column and eluted with a gradient from 0 to 50% ethyl acetate/hexanes) to give 6A (7.39 g, 22.08 mmol, 82% yield) as a white solid. MS (ESI) m/z: 335.1 [M+1]+; 1H NMR (400 MHz, chloroform-d) δ ppm 7.97-8.13 (m, 2H) 7.55 (d, J=7.53 Hz, 1H) 7.27-7.45 (m, 5H) 5.11-5.26 (m, 2H) 4.58-4.72 (m, 2H) 3.03 (br. s., 3H), 3:2 rotamers.

1. temperaturecooled to 0° C.
2. stirringThe mixture was stirred at rt for 30 min
3. concentrationwas concentrated
4. dissolutionThe residue was dissolved in THF (50 mL)
5. additiontreated with water (20 mL) and sat. NaHCO3 (20 mL)
6. stirringAfter stirring for 10 min
7. stirringThe mixture was stirred at rt over night
8. customTHF was removed under reduced pressure
9. extractionThe mixture was extracted with EtOAc (2×)
10. washThe organic phase was washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated
13. customThe crude product was purified by flash chromatography (
14. washeluted with a gradient from 0 to 50% ethyl acetate/hexanes)

ORD record

ord-0aa649a07293401b88873da69dd6ff87

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174974B2