Dimethylformamide → 2-(2-Methoxy-4-nitrophenoxy)-1-(pyrrolidin-1-yl)ethanone

HRID 2420699Notes

Reaction equation

HRID 2420699 reaction equation
CN(C=O)C.[OH:6][CH2:7][C:8]([N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:9].Cl[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[O:25][CH3:26]>O>[CH3:26][O:25][C:17]1[CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=[CH:21][C:16]=1[O:6][CH2:7][C:8]([N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:9]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 705192-Chloro-5-nitroanisoleHCID 64804852-Hydroxy-1-(pyrrolidin-1-yl)ethan-1-one

Product 1

HCID 672146952-(2-Methoxy-4-nitrophenoxy)-1-(pyrrolidin-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of DMF (20 mL) containing 2-hydroxy-1-(pyrrolidin-1-yl)ethanone (2.00 g, 15.5 mmol) under N2 was added 60% NaH/paraffin (640 mg, 16 mmol). Once gas evolution ceased, 2-chloro-5-nitroanisole (1.9 g, 10 mmol) was added. After stirring for 18 hr at 20°, the reaction was diluted with H2O prior to being extracted with EtOAc 3×. The organic layers were washed twice with aq. Na2CO3, brine and dried over Na2SO4 prior to concentration. Chromatography on silica gel using 25% EtOAc/CH2Cl2 eluted 2.06 g of 2(2-methoxy-4-nitrophenoxy)-1-(pyrrolidin-1-yl)ethanone (52%). 1H NMR (DMSO-d6) δ 1.73-1.79 (m, 2H), 1.86-1.92 (m, 2H), 3.29-3.32 (m, 2H), 3.43-3.46 (m, 2H), 3.04 (s, 3H), 4.93 (s, 2H), 7.02 (d, J=8.80 Hz, 1H), 7.73 (d, J=2.74 Hz, 1H), 7.84 (dd, J=8.80 Hz, 2.20 Hz, 1H); 13C NMR (DMSO-d6) δ 23.22, 25.35, 44.27, 45.30, 55.76, 66.23, 106.35, 111.93, 116.99, 140.51, 148.25, 153.28, 164.33; HPLC a) column: PHENOMENEX® C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.2% H3PO4 to 90% MeOH/10% H2O/0.2% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 2.24 min retention time, (100%); HPLC b) column: PHENOMENEX® C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 2.29 min retention time; MS (ES): m/z 281 (M+H)+.

Workup

  1. extractionto being extracted with EtOAc 3×
  2. washThe organic layers were washed twice with aq. Na2CO3, brine
  3. dry with materialdried over Na2SO4
  4. concentrationto concentration
  5. washChromatography on silica gel using 25% EtOAc/CH2Cl2 eluted 2.06 g of 2(2-methoxy-4-nitrophenoxy)-1-(pyrrolidin-1-yl)ethanone (52%)
  6. customC18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.2% H3PO4
  7. custom1 min
  8. customat 220 nm, 2.24 min retention time, (100%)
  9. customC18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA
  10. customto 90% MeOH/10% H2O/0.1% TFA, 1 min
  11. customat 220 nm, 2.29 min retention time

Sources & evidence

ORD record
ord-60a27a5e13d4450e88dcf89318db1c6b
Source dataset
uspto-grants-2011_06
Patent number
US07956049B2

Reaction notes

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