Triethylamine → (R)-4-Bromo-N-(1-morpholinopropan-2-yl)-2-nitroaniline

HRID 1670603Notes

Reaction equation

HRID 1670603 reaction equation
Cl.[CH3:2][C@@H:3]([NH2:11])[CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[Br:12][C:13]1[CH:14]=[CH:15][C:16](F)=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=1.C(N(CC)CC)C>C(OCC)(=O)C.CN(C1C=CC=CN=1)C>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([NH:11][C@H:3]([CH3:2])[CH2:4][N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27363284-Bromo-1-fluoro-2-nitrobenzeneHCID 67310127(R)-1-Morpholinopropan-2-amine hydrochloride

Product 1

HCID 67334620(R)-4-Bromo-N-(1-morpholinopropan-2-yl)-2-nitroanilineYield 95%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

Reflux a mixture of (R)-1-methyl-2-morpholin-4-yl-ethylaminehydrochloride (0.04 mol, 8.7 g), 5-bromo-2-fluoronitrobenzene (0.048 mol, 10.5 g), triethylamine (0.20 mol, 20.2 g) and dimethylaminopyridine (0.0004 mol, 0.048 g) in ethyl acetate (220 mL) for 16 h. Cool the reaction mixture to room temperature, dilute with ethyl acetate, and wash with water and brine. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate. Purify on a silica gel column using 10% ethyl acetate in hexanes as eluent to obtain the title compound (12.8 g, 95%) as an orange solid. 1H NMR (400 MHz, CDCl3) δ 1.29 (d, 3H), 2.47-2.51 (m, 5H), 2.53-2.58 (m, 1H), 3.64-3.69 (m, 4H), 3.72-3.78 (m, 1H), 6.78 (d, 1H), 7.46 (dd, 1H), 8.30 (d, 1H), 8.33 (d, 1H).

Workup

  1. temperatureReflux
  2. washwash with water and brine
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify on a silica gel column

Sources & evidence

ORD record
ord-4f68c2598c6d49e8ad624edfb45b6b06
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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