Dimethylformamide → 4-methoxy-3-[2-(1-pyrrolidinyl)ethoxy]Benzenamine

HRID 1987900Notes

Reaction equation

HRID 1987900 reaction equation
CN(C=O)C.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][C:9]=1[OH:17].Cl.Cl[CH2:20][CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.C([O-])([O-])=O.[K+].[K+]>O>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][C:9]=1[O:17][CH2:20][CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 694712-Methoxy-5-nitrophenolHCID 816681-(2-Chloroethyl)pyrrolidine hydrochloride

Product 1

HCID 189801284-methoxy-3-[2-(1-pyrrolidinyl)ethoxy]BenzenamineYield 87%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred DMF suspension (5 mL) of 2-methoxy-5-nitrophenol (0.5 g, 2.96 mmol), 1-(2-chloroethyl)pyrrolidine hydrochloride (0.75 g (4.43 mmol) and K2CO3 (1.02 g, 7.4 mmol) was heated at 80° C. for 2 hr. After cooling to RT, the reaction was diluted with 20 mL of H2O and extracted with EtOAc (3×20 mL). The combined EtOAc layers were washed brine and dried over MgSO4. After concentration under vacuum, the resulting residue was chromatographed on silica gel. Gradient elution CH2Cl2 to 10% MeOH/CH2Cl2 eluted N-(2-(2-methoxy-5-nitrophenoxy)ethyl)pyrrolidine (507 mg) as a light orange solid. Subsequent conversion of the aryl nitro substituent to the title aryl amine was accomplished in 87% yield following the procedure described in step C of Example 6. MS (ESI) 237 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe combined EtOAc layers were washed brine
  3. dry with materialdried over MgSO4
  4. concentrationAfter concentration under vacuum
  5. customthe resulting residue was chromatographed on silica gel
  6. washGradient elution CH2Cl2 to 10% MeOH/CH2Cl2
  7. washeluted N-(2-(2-methoxy-5-nitrophenoxy)ethyl)pyrrolidine (507 mg) as a light orange solid

Sources & evidence

ORD record
ord-8652013f32a9424cb7fde6af811ed43f
Source dataset
uspto-grants-2009_06
Patent number
US07553836B2

Reaction notes

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