Water → HCID 71209471, compound

HRID 1912532Notes

Reaction equation

HRID 1912532 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3=[N:12][C:13]([CH3:27])=[C:14]([C:23](OC)=[O:24])[C:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>O1CCCC1>[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3=[N:12][C:13]([CH3:27])=[C:14]([CH2:23][OH:24])[C:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 71209421HCID 71209421, compound

Product 1

HCID 71209471HCID 71209471, compoundYield 103.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

An ice cold solution of methyl 1-(4-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (2.2236 g, 5.72 mmol) in tetrahydrofuran (THF) (48.7 ml) was treated slowly with LAH (1M in THF) (17.17 ml, 17.17 mmol), and then warmed to rt overnight. The reaction was cooled to 0° C., treated slowly with 652 uL H2O, followed by 652 uL 20% aq. NaOH and 3×652 uL H2O. The mixture was stirred at rt for 1 hour, filtered, washed with Et2O and EtOAc, and then concentrated to give crude (1-(4-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol (2.1421 g) as light yellow solid. The intermediate was suspended in dichloromethane (DCM) (48.7 ml), treated with PCC (1.851 g, 8.59 mmol), and stirred at rt for 18 hours. The mixture was filtered through Celite™, washed with DCM and EtOAc, and then concentrated. Purification with column chromatography (0-40% EtOAc/Hexane) afforded 1-(4-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (1.68 g, 4.70 mmol, 82% yield) as off white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.08 (s, 1 H), 7.38-7.29 (m, 4 H), 7.30-7.23 (m, 2 H), 7.10 (d, J=3.6 Hz, 1 H), 7.04-6.97 (m, 2 H), 6.35 (d, J=3.6 Hz, 1 H), 5.49 (s, 2 H), 2.96 (s, 3 H), 2.46 (s, 3 H); LCMS (m/z) ES+=359 (M+1).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. filtrationfiltered
  3. washwashed with Et2O and EtOAc
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-1ec1e497f25747498ee44d12d006184f
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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