Hydrochloric Acid → ethyl 1-tosyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 2170989Notes

Reaction equation

HRID 2170989 reaction equation
[S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[Li]CCCC.[C:25](Cl)(=[O:29])[O:26][CH2:27][CH3:28].Cl>C1COCC1.O>[S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH:13]=[C:12]1[C:25]([O:26][CH2:27][CH3:28])=[O:29])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 679757621-tosyl-1H-pyrrolo[3,2-c]pyridineHCID 178418339Butyllithium

Product 1

HCID 67975542ethyl 1-tosyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of compound 6-b (10 g, 367 mmol) in dry THF (150 mL) was cooled to −70° C. and n-BuLi (CAS 109-72-8) (2.5 M in hexane, 16.7 mL, 41.9 mmol) was added dropwise under N2. The mixture was stirred at −78° C. for 1 hour and then ethyl carbonochloridate (CAS 541-41-3) (fresh redistilled, 4.2 mL, 44 mmol) was added dropwise at −70° C. The mixture was warmed to 20° C. naturally and stirred at 20° C. for 1 hour. Then water (800 mL) was added. The mixture was acidified to pH=4 to 5 with a 1N HCl aqueous solution and extracted with ethyl acetate (400 mL×2). Then the pH of the aqueous layer was adjusted to pH=8 by addition of NaHCO3. The resulting mixture was extracted with ethyl acetate (200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and evaporated. The residue was washed with tert-butylmethyl ether. The solid was dried under high vacuum. The residue was purified by flash column chromatography, eluting with petroleum ether/ethyl acetate (3:2). After evaporation of the fractions, 6-c is obtained (6 g, 47%).

Workup

  1. temperatureThe mixture was warmed to 20° C. naturally
  2. stirringstirred at 20° C. for 1 hour
  3. extractionextracted with ethyl acetate (400 mL×2)
  4. additionThen the pH of the aqueous layer was adjusted to pH=8 by addition of NaHCO3
  5. extractionThe resulting mixture was extracted with ethyl acetate (200 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. washThe residue was washed with tert-butylmethyl ether
  10. customThe solid was dried under high vacuum
  11. customThe residue was purified by flash column chromatography
  12. washeluting with petroleum ether/ethyl acetate (3:2)
  13. customAfter evaporation of the fractions

Sources & evidence

ORD record
ord-da028c49af634f14b8e2b38180eda17b
Source dataset
uspto-grants-2015_06
Patent number
US09051317B2

Reaction notes

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