Triphenylphosphine → Methyl 5-(but-2-yn-1-yloxy)picolinate

HRID 930472Notes

Reaction equation

HRID 930472 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.[CH2:12](O)[C:13]#[C:14][CH3:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C(Cl)Cl>[CH2:12]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1)[C:13]#[C:14][CH3:15]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 129912-Butyn-1-olHCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 58449213Methyl 5-(but-2-yn-1-yloxy)picolinate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 5-hydroxypyridine-2-carboxylate (1.5 g, 9.8 mmol, Molbridge) in THF (39 ml) under argon was cooled to 0° C. and 2-butyn-1-ol (1.5 ml, 20 mmol, Aldrich), triphenyl phosphine (2.95 g, 11.2 mmol, Aldrich) and diisopropyl azodicarboxylate (2.2 ml, 11.2 mmol, Aldrich) were added consecutively. The reaction mixture was stirred at room temperature for 2 h. Additional diisopropyl azodicarboxylate (1 ml) was added and the reaction mixture was stirred at room temperature for another 1 h. The reaction mixture was diluted with CH2Cl2 and washed with saturated NaHCO3 solution; the aqueous layer was back-extracted with CH2Cl2. The combined organic extracts were dried over MgSO4 and concentrated in vacuo. Purification by silica gel chromatography (0% to 50% EtOAc/Hexanes) afforded the title compound as a light tan solid. MS m/z=206.0 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for another 1 h
  2. washwashed with saturated NaHCO3 solution
  3. extractionthe aqueous layer was back-extracted with CH2Cl2
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (0% to 50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-902476c3627f453984fd3ba6e5179b49
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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