Hydrochloric Acid → 1H-Pyrrolo(2,3-b)pyridine

HRID 1396360Notes

Reaction equation

HRID 1396360 reaction equation
C(O[C:6](=O)[NH:7][C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=1)(C)(C)C.C([Li])CCC.CN(C)C=O.Cl>O1CCCC1>[NH:7]1[C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:13]2[CH:14]=[CH:6]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 117458482-(N-Boc-Amino)-3-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 92221H-Pyrrolo(2,3-b)pyridineYield 134%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

(3-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (5 g, 24 mmol) was dissolved in tetrahydrofuran (96 mL) and cooled in an ice-salt bath to −15° C. Butyl lithium solution (1.6 M in hexanes, 30 mL, 48 mmol) was added drop wise over 30 min. After an additional 1 h, N,N-dimethylformamide (1.9 mL, 34.5 mmol) was added and the reaction mixture warmed to 25° C. over 16 h. The reaction mixture was added very slowly to approximately 150 mL of 6M HCl solution. The resulting mixture was warmed to 55° C. for 2 h, then cooled, the phases separated, and ethyl acetate was added to the aqueous layer. 6M sodium hydroxide solution was slowly added until the pH 6, then the layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined ethyl acetate extracts were washed with sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo to give 1H-pyrrolo[2,3-b]pyridine (3.8 g, 134%) as a brown semisolid. This was used directly in the next step without further purification. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 10.86 (br. s., 1H) 8.28 (dd, J=4.9, 1.5 Hz, 1H) 7.98 (dd, J=7.7, 1.7 Hz, 1H) 7.36 (d, J=3.4 Hz, 1H) 7.10 (dd, J=7.9, 4.9 Hz, 1H) 6.51 (d, J=3.4 Hz, 1H); LCMS (EI/CI) m/z: 119 [M+H].

Workup

  1. temperaturethe reaction mixture warmed to 25° C. over 16 h
  2. temperatureThe resulting mixture was warmed to 55° C. for 2 h
  3. temperaturecooled
  4. customthe phases separated
  5. additionethyl acetate was added to the aqueous layer
  6. addition6M sodium hydroxide solution was slowly added until the pH 6
  7. customthe layers were separated
  8. extractionthe aqueous layer was extracted once more with ethyl acetate
  9. washThe combined ethyl acetate extracts were washed with sodium chloride solution
  10. dry with materialdried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f73fa9e58f034cb1a096d8e7b0b460a7
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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