Methylamine → HCID 118098742, compound

To a solution of 20A (635 mg, 2.61 mmol) in MeOH (10 mL), was added methylamine (33% in EtOH) (0.390 mL, 3.13 mmol). The mixture was stirred at rt for 3 h, then was cooled to 0° C. and treated with NaBH4 (119 mg, 3.13 mmol). The reaction was stirred at 0° C. for 2 h, then was concentrated. The residue was dissolved in THF (10 mL), treated with H2O (10 mL) and sat. NaHCO3 (10 mL). After stirring for 10 min, Boc2O (684 mg, 3.13 mmol) was added. The mixture was stirred at rt for 2 h, then the THF was evaporated. The mixture was extracted with EtOAc (2×). The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (loaded in chloroform onto a 40 g column and eluted with a gradient from 0 to 40% ethyl acetate/hexanes) to give 20B (864 mg, 2.411 mmol, 92% yield) as a pale yellow oil. MS (ESI) m/z: 381.1 [M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 7.80-7.94 (2H, m), 4.68 (2H, d, J=20.6 Hz), 3.60-3.71 (1H, m), 2.92 (3H, d, J=10.5 Hz), 1.53 (5H, s), 1.43 (4H, br. s.), 1.27 (6H, d, J=6.3 Hz), 3:2 ratio of rotamers.

1. temperaturewas cooled to 0° C.
2. stirringThe reaction was stirred at 0° C. for 2 h
3. concentrationwas concentrated
4. dissolutionThe residue was dissolved in THF (10 mL)
5. additiontreated with H2O (10 mL) and sat. NaHCO3 (10 mL)
6. stirringAfter stirring for 10 min
7. stirringThe mixture was stirred at rt for 2 h
8. customthe THF was evaporated
9. extractionThe mixture was extracted with EtOAc (2×)
10. washThe organic phase was washed with H2O and 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 40% ethyl acetate/hexanes)

ORD record

ord-169bb5129d324c309b379b9ddf8aa010

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174974B2