Lithium Hydroxide → 2-[5-Carboxy-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester

HRID 1406389Notes

Reaction equation

HRID 1406389 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:35])[N:19]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:20]=[C:21]([C:23]([O:25]C)=[O:24])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>O1CCCC1.O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:35])[N:19]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:33])[CH3:34])[CH:20]=[C:21]([C:23]([OH:25])=[O:24])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 581173742-[5-Methoxycarbonyl-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester2×

Product 1

HCID 581173092-[5-Carboxy-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Intermediate (1b), 2-[5-methoxycarbonyl-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester (2.88 g, 5.78 mmol) was stirred in a mixture of tetrahydrofuran (40 mL) and water (20 mL). Lithium hydroxide (0.469 g, 11.2 mmol) was added and the reaction stirred at reflux for 2 hours. After cooling the reaction mixture was concentrated in vacuo, and the residue was taken up in water and the pH adjusted to 5 with the careful addition of an aqueous 2M hydrochloric acid solution. This aqueous solution was extracted with dichloromethane (×3), and the combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to afford the desired title compound as a yellow solid 2.30 g, 85%.

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureAfter cooling the reaction mixture
  3. concentrationwas concentrated in vacuo
  4. additionthe pH adjusted to 5 with the careful addition of an aqueous 2M hydrochloric acid solution
  5. extractionThis aqueous solution was extracted with dichloromethane (×3)
  6. washthe combined extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-abbc655c6db046ab91d9758916145bfc
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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