Sodium hydride → 1-(2-(2-Methoxy-4-nitrophenoxy)ethyl)pyrrolidine

HRID 2384860Notes

Reaction equation

HRID 2384860 reaction equation
[H-].[Na+].[N:3]1([CH2:8][CH2:9][OH:10])[CH2:7][CH2:6][CH2:5][CH2:4]1.Cl[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[O:21][CH3:22]>CN(C=O)C.CCOC(C)=O>[CH3:22][O:21][C:13]1[CH:14]=[C:15]([N+:18]([O-:20])=[O:19])[CH:16]=[CH:17][C:12]=1[O:10][CH2:9][CH2:8][N:3]1[CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 705192-Chloro-5-nitroanisoleHCID 762881-Pyrrolidineethanol

Product 1

HCID 179893551-(2-(2-Methoxy-4-nitrophenoxy)ethyl)pyrrolidineYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add NaH (3.2 g, 80 mmol) portionwise to a 0° C. solution of 2-pyrrolidin-1-yl-ethanol (9.4 mL, 80 mmol) in DMF (180 mL). Stir the reaction 15-20 min until gas evolution ceases. Add a solution of 1-chloro-2-methoxy-4-nitro-benzene (15.0 g, 80 mmol) in DMF (100 mL) via cannula. Warm the reaction to 130° C. and stir for approximately 18 h. Cool to RT and dilute with EtOAc (300 mL). Wash with water (2×100 mL). Extract the organic layer with 1 N HCl (3×150 mL). Wash this acidic layer with EtOAc (100 mL) then basify by adding 1 N NaOH (500 mL) until pH=8-9. Extract the now basic aqueous layer with CH2Cl2 (3×150 mL). Dry the organic layer over Na2SO4 and concentrate to provide 8.5 g (40%) of the desired product as an orange solid. MS/ES m/z 267.3 [M+H]+.

Workup

  1. customthe reaction 15-20 min until gas evolution ceases
  2. temperatureWarm
  3. customthe reaction to 130° C.
  4. stirringstir for approximately 18 h
  5. washWash with water (2×100 mL)
  6. extractionExtract the organic layer with 1 N HCl (3×150 mL)
  7. washWash this acidic layer with EtOAc (100 mL)
  8. additionbasify by adding 1 N NaOH (500 mL) until pH=8-9
  9. extractionExtract the now basic aqueous layer with CH2Cl2 (3×150 mL)
  10. dry with materialDry the organic layer over Na2SO4
  11. concentrationconcentrate

Sources & evidence

ORD record
ord-64e718eeb9ce441c9f08b5b7cf0d97b9
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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