N-methyl-2-pyrrolidone → 1-(3-Methoxy-4-nitrophenylamino)-2-methylpropan-2-ol

HRID 1804701Notes

Reaction equation

HRID 1804701 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.[NH2:13][CH2:14][C:15]([CH3:18])([OH:17])[CH3:16].CN1CCCC1=O.CCN(C(C)C)C(C)C>O>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([NH:13][CH2:14][C:15]([CH3:18])([OH:17])[CH3:16])[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 951022-Propanol, 1-amino-2-methyl-HCID 27792505-Fluoro-2-nitroanisole

Product 1

HCID 651093581-(3-Methoxy-4-nitrophenylamino)-2-methylpropan-2-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A 20 mL reaction vial equipped with a stir bar was charged with 4-fluoro-2-methoxy-1-nitrobenzene (0.5 g, 2.92 mmol), 1-amino-2-methylpropan-2-ol (0.313 g, 3.51 mmol), N-methyl-2-pyrrolidinone (7.3 mL) and Hunig's base (N,N-diisopropylethylamine) (0.76 g, 5.84 mmol). The vessel was sealed and the reaction was heated on a thermal block at 80° C. for 24 hours. The reaction was cooled to ambient temperature, treated with water (40 mL) and extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with brine (2×25 mL), dried over Na2SO4, filtered, and concentrated. The concentrate was purified by flash chromatography on a 10 g silica gel column eluting with 1% methanol/CH2Cl2 to provide the title compound. 1H NMR (500 MHz, dimethylsulfoxide-d6) δ ppm 1.16 (s, 6H) 3.10 (d, 2H) 3.84 (s, 3H) 4.58 (s, 1H) 6.35 (m, 2H) 6.96 (m, 1H) 7.83 (d, 1H).

Workup

  1. customA 20 mL reaction
  2. customvial equipped with a stir bar
  3. customThe vessel was sealed
  4. temperatureThe reaction was cooled to ambient temperature
  5. extractionextracted with ethyl acetate (3×60 mL)
  6. washThe combined organic layers were washed with brine (2×25 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe concentrate was purified by flash chromatography on a 10 g silica gel column
  11. washeluting with 1% methanol/CH2Cl2

Sources & evidence

ORD record
ord-9346fde1e6684ddca317460ff6b92c3b
Source dataset
uspto-grants-2013_01
Patent number
US08354422B2

Reaction notes

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