Hydrochloric Acid → 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylic acid

HRID 1640063Notes

Reaction equation

HRID 1640063 reaction equation
[CH3:1][O:2][C:3]1[C:12]([CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]([O:32]C)=[O:31])[CH:28]=4)[CH:23]=[CH:22]3)[CH2:17][CH2:16]2)=[C:11]2[C:6]([C:7](=[O:36])[CH2:8][C:9]([CH3:35])([CH3:34])[O:10]2)=[CH:5][CH:4]=1.[OH-].[Na+].CO.Cl>O1CCCC1>[CH3:1][O:2][C:3]1[C:12]([CH2:13][CH2:14][N:15]2[CH2:16][CH2:17][CH:18]([N:21]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]([OH:32])=[O:31])[CH:28]=4)[CH:23]=[CH:22]3)[CH2:19][CH2:20]2)=[C:11]2[C:6]([C:7](=[O:36])[CH2:8][C:9]([CH3:34])([CH3:35])[O:10]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887Methanol2×HCID 14798Sodium Hydroxide2×HCID 59439452methyl 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylate

Product 1

HCID 594394671-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

3.5 g of the above crude product of methyl 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylate was dissolved in 28.0 mL of tetrahydrofuran and added with 14 mL of 1 N aqueous sodium hydroxide. 14 mL of methanol was added and the mixture was heated to 40° C. and stirred for 30 minutes. 7 mL of tetrahydrofuran and 3.5 mL of methanol were added and the mixture was stirred for 2 hours and further stirred at the same temperature for about 16 hours. When the reaction mixture was cooled with an ice-water bath and the pH was adjusted to 7 with 12.2 mL of 1 N hydrochloric acid and 0.5 mL of 1 N sodium hydroxide, crystals precipitated. 10 mL of water was further added to this slurry, and crystals were obtained by filtration and the crystals were washed with 21 mL of a mixture of 2-propanol and water (5:1). The crystals were dried in vacuo and 2.45 g of the title compound was obtained.

Workup

  1. stirringthe mixture was stirred for 2 hours
  2. stirringfurther stirred at the same temperature for about 16 hours
  3. temperatureWhen the reaction mixture was cooled with an ice-water bath
  4. customprecipitated
  5. addition10 mL of water was further added to this slurry
  6. customcrystals were obtained by filtration
  7. washthe crystals were washed with 21 mL of a mixture of 2-propanol and water (5:1)
  8. customThe crystals were dried in vacuo

Sources & evidence

ORD record
ord-f3ea93be13f34635a5ba3bdf632d8226
Source dataset
uspto-grants-2012_02
Patent number
US08110688B2

Reaction notes

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