Methanol → HCID 58745798, compound

HRID 1364966Notes

Reaction equation

HRID 1364966 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.[OH-].[K+].CO.[C:17]1(=O)[CH2:21][CH2:20][CH2:19][CH2:18]1>O>[C:17]1([C:3]2[C:4]3[C:9](=[CH:8][C:7]([C:10]([OH:12])=[O:11])=[CH:6][CH:5]=3)[NH:1][CH:2]=2)[CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8452CyclopentanoneHCID 14797Potassium HydroxideHCID 5952301H-indole-6-carboxylic acid

Product 1

HCID 58745798HCID 58745798, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
75 °C

Procedure

A 3 L three-necked flask equipped with a mechanical stirrer was charged with indole 6-carboxylic acid (220 g, 1.365 mole) and KOH pellets (764.45 g, 13.65 mole, 10 equivalents). Water (660 mL) and MeOH (660 mL) were added and the mixture heated to 75° C. Cyclopentanone (603.7 mL, 6.825 mole, 5 equivalents) was added dropwise over 18 h using a pump. The reaction mixture was heated for an additional 3 h (after which the reaction was judged complete by HPLC) and cooled to 0° C. for 1 h. The precipitated potassium salt is collected by filtration, and washed with TBME (2×500 mL) to remove cyclopentanone self-condensation products. The brown solid was re-dissolved in water (2.5 L) and the solution washed with TBME (2×1 L). Following acidification to pH 3 with conc. HCl (425 mL), the beige precipitate was collected by filtration, washed with water (2×1 L) and dried under vacuum at 70° C. The crude product weighed 275.9 g (88.9% mass recovery) and had an homogeneity of 85% (HPLC).

Workup

  1. customA 3 L three-necked flask equipped with a mechanical stirrer
  2. temperatureThe reaction mixture was heated for an additional 3 h (after which the reaction
  3. temperaturecooled to 0° C. for 1 h
  4. filtrationThe precipitated potassium salt is collected by filtration
  5. washwashed with TBME (2×500 mL)
  6. customto remove
  7. customcyclopentanone self-condensation products
  8. washthe solution washed with TBME (2×1 L)
  9. filtrationthe beige precipitate was collected by filtration
  10. washwashed with water (2×1 L)
  11. customdried under vacuum at 70° C

Sources & evidence

ORD record
ord-688554b0619b4433bea6c483e6743b46
Source dataset
uspto-grants-2011_02
Patent number
US07888363B2

Reaction notes

Loading…