Chloroacetaldehyde → HCID 89793959, compound

Temperature

50 °C

(R)-tert-butyl 4-((tert-butoxycarbonyl)amino)-3-oxohexanoate (505a, 7.41 g, 24.59 mmol) was treated with ammonia (2M in MeOH, 123 mL, 246 mmol) and ammonium acetate (14.21 g, 184 mmol) at RT. The resulting mixture was stirred for at 50° C. for 30 min, then treated with chloroacetaldehyde (50 wt % in water, 15.82 mL, 123 mmol) and stirred at 50° C. for 2 h. The reaction mixture was then stirred at RT overnight. The reaction mixture was concentrated to remove most of MeOH and partitioned between sat'd NaHCO3 (100 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (2×50 mL), and the combined organics were washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give a brown residue. It was purified on an ISCO Combiflash RF (160 g Thomson SingleStep column, 0-10% EtOAc in DCM) affording (R)-tert-butyl 2-(1-((tert-butoxycarbonyl)amino)propyl)-1H-pyrrole-3-carboxylate (505b, 4.58 g, 14.12 mmol, 57.4% yield) as a light yellow viscous oil. m/z (ESI, +ve) 347.1 (M+Na)+

1. stirringstirred at 50° C. for 2 h
2. stirringThe reaction mixture was then stirred at RT overnight
3. concentrationThe reaction mixture was concentrated
4. customto remove most of MeOH
5. custompartitioned between sat'd NaHCO3 (100 mL) and EtOAc (100 mL)
6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
7. washthe combined organics were washed with water and brine
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give a brown residue
12. customIt was purified on an ISCO Combiflash RF (160 g Thomson SingleStep column, 0-10% EtOAc in DCM)

ORD record

ord-83093946a9db45f69a1e9d42a87ca807

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2