Triphenylphosphine → (S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2095321Notes

Reaction equation

HRID 2095321 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][OH:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:15][C:16]1[CH:17]=[C:18](O)[CH:19]=[N:20][CH:21]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Br:15][C:16]1[CH:21]=[N:20][CH:19]=[C:18]([O:14][CH2:13][C@@H:9]2[CH2:10][CH2:11][CH2:12][N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:17]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 5995293-Bromo-5-hydroxypyridineHCID 643448(S)-(-)-N-Boc-prolinol

Product 1

HCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methanol (1.39 g, 6.9 mmol, 1.5 equiv.), 5-bromo-3-pyridinol (796 mg, 4.6 mmol) and Ph3P (1.80 g, 6.9 mmol, 1.5 equiv.) in anhydrous THF (35 mL) was added diethyl azodicarboxylate (1.09 mL, 6.9 mmol, 1.5 equiv.) dropwise at 0° C. under Ar protection. After stirring at rt for 120 h, the solvent was removed under reduced pressure. The mixture was diluted with hexane/EtOAc 4:1, and the solution was washed with brine and dried over Na2SO4. After evaporation, the residue was purified by CC (SiO2, hexane/EtOAc 4:1, then 1:1) to afford 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (1.41 g, 86%) as a pale yellow oil, which solidified upon storage at room temperature.

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionThe mixture was diluted with hexane/EtOAc 4:1
  3. washthe solution was washed with brine
  4. dry with materialdried over Na2SO4
  5. customAfter evaporation
  6. customthe residue was purified by CC (SiO2, hexane/EtOAc 4:1

Sources & evidence

ORD record
ord-978b8eaa936743f6bc409b475650d1f8
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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