Sodium Hydroxide → HCID 21347699, compound

HRID 2186349Notes

Reaction equation

HRID 2186349 reaction equation
[OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[C:8]2[CH2:15][CH2:16][CH2:17][C@@H:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=2)[CH2:20][C@@H:19]1[C:34]([O:36]C)=[O:35]>CO>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[C:8]2[CH2:15][CH2:16][CH2:17][C@@H:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=2)[CH2:20][C@@H:19]1[C:34]([OH:36])=[O:35]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 86758153HCID 86758153, compound

Product 1

HCID 21347699HCID 21347699, compoundYield 81.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

0.9 cm3 of 5N aqueous sodium hydroxide was added to a solution of 0.58 g of methyl (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(3-fluorophenyl)propyl]piperidine-3-carboxylate in 21 cm3 of methanol and then the mixture was heated at a temperature in the region of 60° C. for 20 hours, on conclusion of which 0.2 cm3 of 5N aqueous sodium hydroxide was added. Heating was subsequently continued for 3 hours. After cooling to a temperature in the region of 25° C., the solution was evaporated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The residue was taken up in 30 cm3 of water and then treated with 7.8 cm3 of 1N hydrochloric acid. After extracting the aqueous phase with 5 times 10 cm3 of dichloromethane, the aqueous phase was evaporated to dryness under reduced pressure (1 kPa) at a temperature in the region of 60° C. The residue obtained was triturated in 10 cm3 of a dichloromethane/methanol (90/10 by volume) mixture. The insoluble material was filtered off and then the cake was washed with 2 times 5 cm3 of the same mixture. The filtrate was dried over sodium sulfate and then evaporated to dryness under reduced pressure (1 kPa) at a temperature in the region of 40° C. 0.46 g of (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(3-fluorophenyl)propyl]piperidine-3-carboxylic acid was obtained in the form of a foamy solid with a pale yellow color which melts at approximately 206° C.

Workup

  1. additionwas added
  2. temperatureHeating
  3. customthe solution was evaporated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  4. additiontreated with 7.8 cm3 of 1N hydrochloric acid
  5. extractionAfter extracting the aqueous phase with 5 times 10 cm3 of dichloromethane
  6. customthe aqueous phase was evaporated to dryness under reduced pressure (1 kPa) at a temperature in the region of 60° C
  7. customThe residue obtained
  8. customwas triturated in 10 cm3 of a dichloromethane/methanol (90/10 by volume) mixture
  9. filtrationThe insoluble material was filtered off
  10. washthe cake was washed with 2 times 5 cm3 of the same mixture
  11. dry with materialThe filtrate was dried over sodium sulfate
  12. customevaporated to dryness under reduced pressure (1 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-6175f091e50547edbbd572d7a982d4f1
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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