Methyl 6-chloro-5-nitronicotinate → (S)-methyl 6-((1-ethoxy-1-oxopropan-2-yl)(isopropyl)amino)-5-nitronicotinate

HRID 69605

Reaction equation

HRID 69605 reaction equation
[CH:1]([NH:4][C@@H:5]([CH3:11])[C:6]([O:8][CH2:9][CH3:10])=[O:7])([CH3:3])[CH3:2].Cl[C:13]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1>CCOC(C)=O>[CH2:9]([O:8][C:6](=[O:7])[C@@H:5]([N:4]([CH:1]([CH3:3])[CH3:2])[C:13]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1)[CH3:11])[CH3:10]

Participants

4

Reactant 2

HCID 346961Methyl 6-chloro-5-nitronicotinateHCID 45086712(S)-ethyl 2-(isopropylamino)propanoate

Product 1

HCID 58324420(S)-methyl 6-((1-ethoxy-1-oxopropan-2-yl)(isopropyl)amino)-5-nitronicotinateYield 42%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

(S)-ethyl 2-(isopropylamino)propanoate (2.83 g, 17.8 mmol) was added to methyl 6-chloro-5-nitronicotinate (1.72 g, 7.94 mmol) and the reaction mixture was stirred in a closed vial at 90° C. for 20 h. It was cooled and diluted with EtOAc (25 mL). The resulting precipitate was filtered off, the filtrate was concentrated in vacuo and purified using flash column chromatography on silica gel (220 g SiO2, hexanes:ethyl acetate 4:1) to afford the title compound as yellow oil (1.12 g, 42%). 1H NMR (400 MHz, CHLOROFORM-d) δ (ppm): 1.18 (t, J=7.07 Hz, 3 H) 1.30 (d, J=6.32 Hz, 3 H) 1.36 (d, J=6.57 Hz, 3 H) 1.66 (d, J=6.82 Hz, 3 H) 3.48-3.62 (m, 1 H) 3.90 (s, 3 H) 4.03 (q, J=6.65 Hz, 1 H) 4.06-4.21 (m, 2 H) 8.54 (d, J=2.02 Hz, 1 H) 8.70 (d, J=2.02 Hz, 1 H); [M+H] calc'd for C15H21N3O6, 340; found, 340.

Workup

  1. temperatureIt was cooled
  2. filtrationThe resulting precipitate was filtered off
  3. concentrationthe filtrate was concentrated in vacuo
  4. custompurified

Sources & evidence

ORD record
ord-a6f43525adcc4780807da5abb6d2dae9
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Linked notes

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