Chloroacetaldehyde → HCID 89783140, compound
Reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10](=O)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH3:20].Cl[CH2:22][CH:23]=O.O>>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[NH:20][CH:22]=[CH:23][C:11]=1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- 40 °C
Procedure
Tert-butyl 4-((tert-butoxycarbonyl)amino)-3-oxobutanoate (755 g, 2.76 mol) was treated with ammonia (2 M in MeOH, 7.0 L) and NH4OAc (851 g, 11.04 mol) at RT. The resulting mixture was heated at 40° C. for 1 h, then treated with chloroacetaldehyde, 50% in water (1083 g, 5.52 mol, Sinopharm Chemical Reagent Co., Ltd, China) and stirred at 50° C. for 4 h and cooled to RT. The solvent was removed in vacuo and the crude material was diluted with water and EtOAc (water: EtOAc=1:1,5 L: 5 L). The organic layer was separated, dried (Na2SO4) and concentrated. Similarly another 2 batches were carried out on 755 g scale. The combined residue was purified by flash column chromatography (eluted by 5-20% EtOAc in petroleum ether) to afford tert-butyl 2-(((tert-butoxycarbonyl)amino)methyl)-1H-pyrrole-3-carboxylate (820 g, 32% yield). 1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 6.91 (s, 1H), 6.58-6.57 (m, 1H), 6.26-6.24 (m, 1H), 4.34-4.33 (m, 2H), 1.44 (s, 9H), 1.36 (s, 9H).
Workup
- temperaturecooled to RT
- customThe solvent was removed in vacuo
- additionthe crude material was diluted with water and EtOAc (water: EtOAc=1:1,5 L: 5 L)
- customThe organic layer was separated
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customThe combined residue was purified by flash column chromatography (eluted by 5-20% EtOAc in petroleum ether)
Sources & evidence
- ORD record
- ord-a67017f0e5ca461083dfc9bf741684e3
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394297B2
Reaction notes
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