Benzyl Bromide → 1-benzyl-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carbaldehyde

HRID 628291Notes

Reaction equation

HRID 628291 reaction equation
C([O-])([O-])=O.[K+].[K+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Cl:15][C:16]1[N:21]=[C:20]2[CH:22]=[C:23]([CH:34]=[O:35])[N:24](S(C3C=CC=CC=3)(=O)=O)[C:19]2=[CH:18][CH:17]=1>CN(C=O)C>[CH2:7]([N:24]1[C:19]2[C:20](=[N:21][C:16]([Cl:15])=[CH:17][CH:18]=2)[CH:22]=[C:23]1[CH:34]=[O:35])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 1181598205-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine-2-carbaldehyde

Product 1

HCID 1181596031-benzyl-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carbaldehydeYield 102.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

K2CO3 (0.39 g, 2.8 mmol) and benzyl bromide (0.12 mL, 1.0 mmol) were added to a solution of 5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carbaldehyde (0.17 g, 0.94 mmol, from Step 1) in DMF (3.6 mL). After 15 minutes, the reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with two portions of water, one portion of brine, then dried over sodium sulfate, filtered and concentrated to afford 0.26 g of crude 1-benzyl-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carbaldehyde as a yellow solid. Sodium tetrahydroborate (53 mg, 1.4 mmol) was added to a solution of the crude aldehyde in THF (5.0 mL) and EtOH (5.0 mL). After 15 minutes, the reaction mixture was quenched with saturated NH4Cl, and was extracted with EtOAc. The extracts were washed with water followed by brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes afforded purified product as a white solid (0.21 g, 82%). 1H NMR (300 MHz, CDCl3) δ 7.45 (d, J=8.6 Hz, 1H), 7.33-7.25 (m, 3H), 7.06 (d, J=8.6 Hz, 1H), 7.03-6.88 (m, 2H), 6.66 (s, 1H), 5.47 (s, 2H), 4.78 (s, 2H).

Workup

  1. customthe reaction mixture was partitioned between EtOAc and water
  2. washthe organic layer was washed with two portions of water, one portion of brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a15b407fe271428aa5f97a0e306469ba
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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