Toluene → HCID 53627624, compound

HRID 1876686Notes

Reaction equation

HRID 1876686 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[CH:12]=[CH:11][NH:10][C:7]2=[N:8][CH:9]=1.C1(C)C=CC=CC=1.Br[CH2:21][C:22]([O:24]C)=[O:23]>O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:3][C:4]1[CH:5]=[C:6]2[CH:12]=[CH:11][N:10]([CH2:21][C:22]([OH:24])=[O:23])[C:7]2=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 60984Methyl bromoacetateHCID 242292135-Chloro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 53627624HCID 53627624, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of NaOH (5.19 g, 129.8 mmol) in water (10 mL) was added tetrabutylammonium bromide (0.35 g, 1.08 mmol), 5-chloro-1H-pyrrolo[2,3-b]pyridine (1.5 g, 9.83 mmol), toluene (60 mL) and methyl 2-bromoacetate (9 g, 59 mmol). The reaction was heated overnight at 100° C. The reaction was quenched with water, the layers were separated and the aqueous layer was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated. 2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)acetate solution in THF was treated with NaOH and stirred at RT for 5 hours. The reaction mixture was then diluted with water and the pH was adjusted to 1 with 1N HCl to crash out the product. The reaction was then filtered, azeotroped with acetonitrile and dried to give 2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)acetic acid. (2 g, 97% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.18 (d, J=2.3 Hz, 1H), 8.05 (d, J=2.3 Hz, 1H), 7.57 (d, J=3.5 Hz, 1H), 6.42 (d, J=3.5 Hz, 1H), 4.74 (s, 2H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=211.1; tR=1.10 min.

Workup

  1. customThe reaction was quenched with water
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with DCM
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. addition2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)acetate solution in THF was treated with NaOH
  8. additionThe reaction mixture was then diluted with water
  9. filtrationThe reaction was then filtered
  10. customazeotroped with acetonitrile
  11. customdried

Sources & evidence

ORD record
ord-0435e0c15ffd4506b8197c39a4f16f65
Source dataset
uspto-grants-2012_11
Patent number
US08309587B2

Reaction notes

Loading…