Diisopropylethylamine → [1-(3-Amino-5-methyl-4-nitro-phenyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

HRID 970354Notes

Reaction equation

F[C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH2:8])[CH:7]=1.[CH3:13][C:14]([O:17][C:18]([NH:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)=[O:19])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C.C([O-])(O)=O.[Na+]>CS(C)=O>[C:14]([O:17][C:18](=[O:19])[NH:20][CH:21]1[CH2:26][CH2:25][N:24]([C:2]2[CH:3]=[C:4]([CH3:12])[C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH2:8])[CH:7]=2)[CH2:23][CH2:22]1)([CH3:16])([CH3:13])[CH3:15]

Participants

Conditions

Temperature: 85 °C

Procedure

5-Fluoro-3-methyl-2-nitro-phenylamine (0.97 g, 5.7 mmol), 4-N-BOC-aminopiperidine (1.60 g, 8.0 mmol), diisopropylethylamine (2.5 ml, 14 mmol) and DMSO (10 ml) are combined and stirred at 85° C. for 3 hours. The reaction mixture was poured on saturated aqueous NaHCO3 solution and extracted with ethyl acetate. The organic layers were washed with water (3×) and brine, dried over Na2SO4 and concentrated. Flash column chromatography on silica (eluent hexanes-ethyl acetate-triethylamine 50-50-1, then 33-66-1) gave the tiitle compound as a yellow solid. (1.57 g, 79%). LCMS (M+H)+ m/z 351 (t=1.55 min.). 1H NMR (500 MHz, CD3OD) δ 6.70 (1H, broad s), 6.22 (1H, d, J=2.5 Hz)), 6.13 (1H, d, J=2.5 Hz), 3.88 (2H, d, J=13.3 Hz), 3.58 (1H, broad s), 2.98 (2H, t, J=11.8 Hz), 2.48 (3H, s), 1.92 (2H, d, J=11.3 Hz), 1.48 (2H, m), 1.45 (9H, s). Procedure for the Preparation of 3-methyl-5-(2-morpholin-4-ethoxy)-2-nitro phenylamine

Workup

extractionextracted with ethyl acetate
washThe organic layers were washed with water (3×) and brine
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-45866fadfaa44ef6aa6bb5e54cf1a1e5
Source dataset: uspto-grants-2007_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07312215B2

Reaction notes

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