Ammonium Chloride → 1,1-Dimethylethyl (2S)-4-[(4-aminophenyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 906361Notes

Reaction equation

[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4][N:3]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[Cl-].[NH4+]>CO.O.[Fe]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:6]2[CH2:5][CH2:4][N:3]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:2]([CH3:1])[CH2:7]2)=[CH:10][CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To 1,1-dimethylethyl (2S)-2-methyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate (D21) (15 g, 44.8 mol) in MeOH (150 mL) and water (150 mL) at 80° C. was added ammonium chloride (11.9 g, 0.224 mol) and iron powder (7.5 g, 0.134 mol) with vigorous stirring. The reaction was stirred at 80° C. for 2 h then filtered through Celite® while still hot and the filter cake was washed with further DCM. The filtrate layers were separated and the aqueous layer was washed with DCM (×3). The DCM layers were combined, dried (Na2SO4) and concentrated to give the crude product which was purified by column chromatography. Elution with 20-70% EtOAc/petroleum ether gave the title compound as a white solid (9.46 g).

Workup

filtrationthen filtered through Celite® while still hot and the filter cake
washwas washed with further DCM
customThe filtrate layers were separated
washthe aqueous layer was washed with DCM (×3)
dry with materialdried (Na2SO4)
concentrationconcentrated
customto give the crude product which
customwas purified by column chromatography
washElution with 20-70% EtOAc/petroleum ether

Sources & evidence

ORD record: ord-dd4226ac23d1458dbaaf8294a2a462aa
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012981B2

Reaction notes

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