4-Hydroxymethylpyridine → ethyl 1-[(4-pyridyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

HRID 1666290Notes

Reaction equation

HRID 1666290 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7]O)=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:28]1[C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[CH:30]=[C:29]1[C:37]([O:39][CH2:40][CH3:41])=[O:38].N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[N:1]1[CH:2]=[CH:3][C:4]([CH2:7][N:28]2[C:32]3=[N:33][CH:34]=[CH:35][CH:36]=[C:31]3[CH:30]=[C:29]2[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 114724-HydroxymethylpyridineHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 21868741Ethyl 1H-pyrrolo(2,3-b)pyridine-2-carboxylate

Product 1

HCID 67444329ethyl 1-[(4-pyridyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylateYield 74.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

0.51 g (4.73 mmol) of 4-pyridylmethanol and then 1.24 g (4.73 mmol) of triphenyl-phosphine are successively added with stirring to a solution of 0.6 g (3.15 mmol) of ethyl 1H-pyrrolo[2,3-b]pyridine-2-carboxylate, obtained according to the protocol described in step 3.2, in 40 mL of dry tetrahydrofuran, maintained under an inert atmosphere. 0.82 g (4.73 mmol) of diethyl azodicarboxylate is then added dropwise at 0° C. The reaction mixture is stirred for 24 hours at room temperature and then concentrated under reduced pressure. A mixture of water and ethyl acetate (20 mL, v/v) is added and the pH of the reaction mixture is adjusted to 5-6 by adding acetic acid. The organic phase separated out is then washed twice with 10 mL of water and once with 10 mL of saturated sodium chloride solution and then dried over magnesium sulfate. After concentrating under reduced pressure, the resulting oil is purified by chromatography on a column of silica gel. 0.66 g of expected product is isolated.

Workup

  1. customobtained
  2. temperaturemaintained under an inert atmosphere
  3. concentrationconcentrated under reduced pressure
  4. additionA mixture of water and ethyl acetate (20 mL, v/v)
  5. additionis added
  6. additionby adding acetic acid
  7. customThe organic phase separated out
  8. washis then washed twice with 10 mL of water and once with 10 mL of saturated sodium chloride solution
  9. dry with materialdried over magnesium sulfate
  10. concentrationAfter concentrating under reduced pressure
  11. customthe resulting oil is purified by chromatography on a column of silica gel

Sources & evidence

ORD record
ord-e540ff05ec87403393fee22ef7432afe
Source dataset
uspto-grants-2011_10
Patent number
US08044066B2

Reaction notes

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