3-Bromo-2-methylpyridine → 3-((3-Bromopyridin-2-yl)methyl)-3-hydroxy-1-isopentyl-5-methylindolin-2-one

HRID 1523047Notes

Reaction equation

HRID 1523047 reaction equation
[Li+].CC([N-]C(C)C)C.[Br:9][C:10]1[C:11]([CH3:16])=[N:12][CH:13]=[CH:14][CH:15]=1.[CH2:17]([N:22]1[C:30]2[C:25](=[CH:26][C:27]([CH3:31])=[CH:28][CH:29]=2)[C:24](=[O:32])[C:23]1=[O:33])[CH2:18][CH:19]([CH3:21])[CH3:20]>>[Br:9][C:10]1[C:11]([CH2:16][C:24]2([OH:32])[C:25]3[C:30](=[CH:29][CH:28]=[C:27]([CH3:31])[CH:26]=3)[N:22]([CH2:17][CH2:18][CH:19]([CH3:20])[CH3:21])[C:23]2=[O:33])=[N:12][CH:13]=[CH:14][CH:15]=1

Participants

4

Reactant 3

HCID 12010033-Bromo-2-methylpyridineHCID 2724682Lithium diisopropylamideHCID 47302421-Isopentyl-5-methylindoline-2,3-dione

Product 1

HCID 904186613-((3-Bromopyridin-2-yl)methyl)-3-hydroxy-1-isopentyl-5-methylindolin-2-oneYield 8%

Conditions

Temperature
-78 °C

Procedure

To a flame dried flask cooled under argon was added freshly prepared LDA (0.82 mL, 0.48 mmol, 0.38M in anhydrous THF). While stirring at −78° C., 3-bromo-2-methylpyridine (50 μL, 0.48 mmol, purchased from Aldrich) was added. The solution stirred at this temperature for two hours at which point a 1-isopentyl-5-methylindoline-2,3-dione (0.045 grams, 0.19 mmol, 0.4 M in THF) was added. The solution was then warmed to room temperature slowly. Once all of the starting material had been consumed, the reaction was quenched with ammonium chloride (saturated), diluted with ethyl acetate, and the organic layer removed. The aqueous layer was salted out using sodium chloride and washed two more times with ethyl acetate. The combined organic material was dried with sodium sulfate, filtered, and concentrated. Purification was done on preparative thin layer chromatography using hexanes/ethyl acetate (2:1) to afford the desired material. (8% Yield). 1H NMR δ 8.53 (dd, 1H), 7.89 (dd, 1H), 7.17-7.09 (m, 3H), 7.03 (d, 1H), 6.73 (d, 1H), 3.83-57 (m, 2H), 3.52 (d, 1H), 3.34 (d, 1H), 2.30 (s, 3H), 1.65 (m, 1H), 1.54 (m, 2H), 0.96 (dd, 6H). Calculated mass for C20H23BrN2O2 402.09, observed, 425.1 (M+Na).

Workup

  1. customTo a flame dried flask
  2. temperaturecooled under argon
  3. additionwas added
  4. temperatureThe solution was then warmed to room temperature slowly
  5. customOnce all of the starting material had been consumed
  6. customthe reaction was quenched with ammonium chloride (saturated)
  7. additiondiluted with ethyl acetate
  8. customthe organic layer removed
  9. washwashed two more times with ethyl acetate
  10. dry with materialThe combined organic material was dried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification

Sources & evidence

ORD record
ord-98a647ebbc4c4cefb05dceff806e1bf4
Source dataset
uspto-grants-2015_07
Patent number
US09079853B2

Reaction notes

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