p-Fluoronitrobenzene → HCID 21132705, compound

HRID 1510272Notes

Reaction equation

HRID 1510272 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[OH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]1.[H-].[Na+]>C1COCC1>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C@H:12]([O:11][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:13]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 21132705HCID 21132705, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Fluoronitrobenzene (2.82 g, 20 mmol) was mixed with (S)-3-hydroxy-N-Boc-pyrrolidine (3.74 g, 20 mmol) in dry THF (100 mL). Sodium hydride (1.69 g, 60% in mineral oil) was added under ice bath and the mixture was stirred for 1 hr. The ice bath was removed and the mixture was stirred at room temperature overnight. Solvents were evaporated and the residue was extracted with ethyl acetate and 0.2N hydrochloric acid. The organic layer was washed with water and brine, dried over sodium sulfate. Solvents were evaporated and the residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexanes, 5% to 60% linear gradient). The desired fraction was concentrated and recrystallized from petroleum ether and ether (3:1 ratio) to give a pale yellow solid as (S)-3-(4-nitro-phenoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (4.33 g, 70.3% yield).

Workup

  1. customThe ice bath was removed
  2. stirringthe mixture was stirred at room temperature overnight
  3. customSolvents were evaporated
  4. extractionthe residue was extracted with ethyl acetate and 0.2N hydrochloric acid
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. customSolvents were evaporated
  8. customthe residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexanes, 5% to 60% linear gradient)
  9. concentrationThe desired fraction was concentrated
  10. customrecrystallized from petroleum ether and ether (3:1 ratio)

Sources & evidence

ORD record
ord-8c7cd4e3d4f24e11b385a2111b39f8e4
Source dataset
uspto-grants-2012_07
Patent number
US08211914B2

Reaction notes

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