Sodium borohydride → (1-benzyl-5-chloro-1H-pyrrolo[3,2-b]pyridin-2-yl)methanol

HRID 628292Notes

Reaction equation

HRID 628292 reaction equation
[BH4-].[Na+].[CH2:3]([N:10]1[C:18]2[C:13](=[N:14][C:15]([Cl:19])=[CH:16][CH:17]=2)[CH:12]=[C:11]1[CH:20]=[O:21])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C1COCC1.CCO>[CH2:3]([N:10]1[C:18]2[C:13](=[N:14][C:15]([Cl:19])=[CH:16][CH:17]=2)[CH:12]=[C:11]1[CH2:20][OH:21])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 1181596031-benzyl-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carbaldehyde

Product 1

HCID 118159445(1-benzyl-5-chloro-1H-pyrrolo[3,2-b]pyridin-2-yl)methanol

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

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 quenched with saturated NH4Cl
  2. extractionwas extracted with EtOAc
  3. washThe extracts were washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washFlash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes
  8. customafforded
  9. custompurified product as a white solid (0.21 g, 82%)

Sources & evidence

ORD record
ord-923d880ba59c4a93b2ed52eda1d6ae5f
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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