Hydrochloric Acid → Ethyl 1-(benzenesulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

HRID 628334Notes

Reaction equation

HRID 628334 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[N:19]=[C:18]2[CH:20]=[CH:21][N:22]([S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:17]2=[CH:16][CH:15]=1.Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34].Cl>C1COCC1>[Cl:13][C:14]1[N:19]=[C:18]2[CH:20]=[C:21]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[N:22]([S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:17]2=[CH:16][CH:15]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 10928Ethyl chloroformateHCID 181764365-Chloro-1-(phenylsulfonyl)-4-azaindoleHCID 178418339Butyllithium

Product 1

HCID 53816579Ethyl 1-(benzenesulfonyl)-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

1.6 M n-Butyllithium in hexanes (9.6 mL, 15 mmol) was added dropwise to a solution of N,N-diisopropylamine (2.3 mL, 16 mmol) in THF (43 mL) at −78° C. Following complete addition, the temperature of the reaction was raised to 0° C. for 30 minutes and then was re-cooled to −78° C. 5-Chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine (3.00 g, 10.2 mmol, from Example 2, Step 1) in THF (8 mL) was added dropwise and the reaction was stirred for 1 hour, at which time ethyl chloroformate (1.4 mL, 14 mmol, Alfa Aesar) was added. The reaction was allowed to stir at −78° C. for 2 hours and was then allowed to warm to room temperature. The mixture was poured into dilute HCl and extracted with three portions of ethyl acetate. The combined extracts were dried over sodium sulfate, decanted, and the solvent was removed in vacuo. Flash chromatography eluting with a gradient from 0-50% EtOAc in hexanes afforded product as an off white solid (1.8 g, 48%).

Workup

  1. additionaddition
  2. temperaturewas re-cooled to −78° C
  3. additionwas added
  4. temperatureto warm to room temperature
  5. extractionextracted with three portions of ethyl acetate
  6. dry with materialThe combined extracts were dried over sodium sulfate
  7. customdecanted
  8. customthe solvent was removed in vacuo
  9. washFlash chromatography eluting with a gradient from 0-50% EtOAc in hexanes afforded product as an off white solid (1.8 g, 48%)

Sources & evidence

ORD record
ord-f064bf910b1c4d2aa9222417d633d1bb
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

Loading…