Sodium Hydroxide → HCID 57810467, compound

HRID 2106063Notes

Reaction equation

HRID 2106063 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]=[CH:12][C:13]([O:15]C)=[O:14])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:17].[OH-].[Na+]>C1COCC1.CO>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9](/[CH:11]=[CH:12]/[C:13]([OH:15])=[O:14])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:17]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66918045HCID 66918045, compound

Product 1

HCID 57810467HCID 57810467, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 3-(5-fluoro-3-methylindol-7-yl)acrylate (1.75 kg, 7.51 mole), prepared as described in Example 1, in 23.4 L THF/MeOH (1:1) at room temperature was added 2 M aqueous sodium hydroxide (16.35 L, 32.7 moles). Stirring was continued for 15 h, then the reaction mixture was concentrated in vacuo to remove the volatile organic solvents. The solution was diluted with 20 L water, then extracted with dichloromethane (3×10 L). The aqueous layer was acidified to a pH of 2-3 with 2 M HCl, which induced precipitation of the product. The product was collected via vacuum filtration, washed with water (2×2 L), and vacuum dried at 60° C. to afford 1.036 kg (91% yield) of the desired title compound: 1H NMR (400 MHz, DMSO-d6) δ 2.23 (d, 3H, J=0.8 Hz), 6.67 (d, 1H, J=16 Hz), 7.24 (br s, 1H), 7.34 (dd, 1H, J=9.2, 2.4 Hz), 7.41 (dd, 1H, J=10.4, 2.4 Hz), 8.06 (dd, 1H, J=16, 1.2 Hz), 11.35 (s, 1H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customto remove the volatile organic solvents
  3. additionThe solution was diluted with 20 L water
  4. extractionextracted with dichloromethane (3×10 L)
  5. customprecipitation of the product
  6. filtrationThe product was collected via vacuum filtration
  7. washwashed with water (2×2 L), and vacuum
  8. customdried at 60° C.

Sources & evidence

ORD record
ord-b2ff71b1ff3a426580453f4029661c2c
Source dataset
uspto-grants-2009_08
Patent number
US07579483B2

Reaction notes

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