Water → 4-Hydroxy-1-(4-nitrophenyl)-pyrrolidine-2-carboxylic acid ethyl ester

HRID 2199401Notes

Reaction equation

HRID 2199401 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH2:11]([O:13][C:14]([CH:16]1[CH2:20][CH:19]([OH:21])[CH2:18][NH:17]1)=[O:15])[CH3:12].C(=O)(O)[O-].[Na+].O>CN(C=O)C.C(OCC)(=O)C>[CH2:11]([O:13][C:14]([CH:16]1[CH2:20][CH:19]([OH:21])[CH2:18][N:17]1[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1)=[O:15])[CH3:12]

Participants

7

Reactant 4

HCID 962WaterHCID 9590p-FluoronitrobenzeneHCID 423727Ethyl 4-hydroxypyrrolidine-2-carboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 695210484-Hydroxy-1-(4-nitrophenyl)-pyrrolidine-2-carboxylic acid ethyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

4-Fluoronitrobenzene (0.28 mL, 2.65 mmol), 4-hydroxy-pyrrolidine-2-carboxylic acid ethyl ester (419 mg, 2.65 mmol), and sodium bicarbonate (222 mg, 2.65 mmol) were dissolved in 5 mL dry DMF and heated to 80° C. After 24 h at this temperature, the reaction was cooled and water and ethyl acetate were added. The organic phase washed with brine, dried (MgSO4), and concentrated. Flash chromatography (65-75% ethyl acetate/hexanes) gave 260 mg (35% yield) of the desired product 1H NMR (CDCl3, 500 MHz) 8.15 (d, J=9.3 Hz, 2H), 6.54 (d, J=9.3 Hz, 2H), 4.60 (m, 1H), 4.41 (d, J=9.2 Hz, 1H), 4.31 (dq, J=10.8, 7.1 Hz, 1H), 4.29 (dq, J=10.8, 7.1 Hz, 1H), 3.73 (dt, J=11.0, 1.2 Hz, 1H), 3.70 (dd, J=11.0, 4.2 Hz, 1H), 2.51 (ddd, J=14.2, 9.2, 4.2 Hz, 1H), 2.35 (dd, J=14.2, 1.2 Hz, 1H), 1.34 (t, J=7.1 Hz, 3H).

Workup

  1. temperaturethe reaction was cooled
  2. washThe organic phase washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c04aa35737524dc8a62836485caa9731
Source dataset
uspto-grants-2016_06
Patent number
US09359285B2

Reaction notes

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