Triphenylphosphine → 2-Methyl-3-nitro-6-(pyrrolidin-3-yloxy)pyridine

HRID 390311Notes

Reaction equation

HRID 390311 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH2:12]1[CH:16](O)[CH2:15][NH:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O>O1CCCC1>[CH3:1][C:2]1[C:3]([N+:9]([O-:11])=[O:10])=[CH:4][CH:5]=[C:6]([O:8][CH:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[N:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 982104-HydroxypyrrolidineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 178433443HCID 178433443, compound

Product 1

HCID 668835522-Methyl-3-nitro-6-(pyrrolidin-3-yloxy)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

6-Methyl-5-nitropyridin-2-ol (5 g) was dissolved in tetrahydrofuran and DL-3-pyrrolidinol (2.83 g) and triphenylphosphine (12.76 g) were added. Di-tert-butyl (E)-diazene-1,2-dicarboxylate (11.21 g) dissolved in tetrahydrofuran (15 mL) was added dropwise over 15 min. The reaction mixture was stirred at room temperature for 50 h. The reaction mixture was concentrated in vacuo. The remaining residue was suspended in dichloromethane and trifluoroacetic acid (7.55 mL) was added dropwise. The reaction mixture was stirred for 12 h at room temperature. The reaction mixture was concentrated in vacuo, redissolved in dichloromethane and extracted several times with 1N hydrochloric acid. The combined aqueous extracts were treated with 1N NaOH to pH 10 and extracted with ethyl acetate (3×). The combined ethyl acetate extracts were successively washed with water and brine and dried (sodium sulfate). After concentration in vacuo, the crude product was purified by flash chromatography (silica, dichloromethane, 1-10% methanol gradient). Yield: 1.5 g (18.6%, pale yellow oil).

Workup

  1. additionwas added dropwise over 15 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiontrifluoroacetic acid (7.55 mL) was added dropwise
  4. stirringThe reaction mixture was stirred for 12 h at room temperature
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. dissolutionredissolved in dichloromethane
  7. extractionextracted several times with 1N hydrochloric acid
  8. additionThe combined aqueous extracts were treated with 1N NaOH to pH 10
  9. extractionextracted with ethyl acetate (3×)
  10. washThe combined ethyl acetate extracts were successively washed with water and brine
  11. dry with materialdried (sodium sulfate)
  12. concentrationAfter concentration in vacuo
  13. customthe crude product was purified by flash chromatography (silica, dichloromethane, 1-10% methanol gradient)

Sources & evidence

ORD record
ord-43f53698f42645c5942f08b3947b3a90
Source dataset
uspto-grants-2013_02
Patent number
US08383641B2

Reaction notes

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