Hydrochloric Acid → HCID 131723282, compound

HRID 2186381Notes

Reaction equation

HRID 2186381 reaction equation
[BH4-].[Na+].[O:3]=[C:4]([C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][CH:27]=1)[CH2:5][CH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][S:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:9][C@@H:8]1[CH2:21][C:22]([O:24][CH3:25])=[O:23].O.[ClH:39]>[OH-].[Na+].CO.C(OCC)C>[ClH:39].[ClH:39].[OH:3][CH:4]([C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][CH:27]=1)[CH2:5][CH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][S:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:9][C@@H:8]1[CH2:21][C:22]([O:24][CH3:25])=[O:23]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 4311764Sodium borohydrideHCID 131723284HCID 131723284, compound

Product 1

HCID 131723282HCID 131723282, compound

Reagents, catalysts & solvents 3

HCID 14798Sodium HydroxideCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

1 drop of 5N aqueous sodium hydroxide solution and then, portionwise, 0.17 g of sodium borohydride were added, with stirring, to a solution, maintained at a temperature in the region of 20 ° C., of 0.84 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate in 12 cm3 of methanol. The mixture was stirred for 3 hours at a temperature in the region of 20° C. After adding 10 cm3 of water, the methanol was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was extracted with 2 times 20 cm3 of dichloromethane and then the combined extracts were washed with 2 times 30 cm3 of water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. An oil was obtained, which oil was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 2.5 cm; silica volume 150 cm3), elution was carried out with a dichloromethane/methanol (99/1 by volume) mixture. Fractions 56 to 115 were combined and then concentrated as above. An oil was obtained, the hydrochloride of which was prepared in the following way: the oil was dissolved in 20 cm3 of diethyl ether and then poured onto 2 cm3 of a 1 N solution of hydrochloric acid in ether. The precipitate formed was filtered off and dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 40° C. 0.3 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate dihydrochloride was obtained in the form of a white solid.

Workup

  1. stirringThe mixture was stirred for 3 hours at a temperature in the region of 20° C
  2. customthe methanol was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. extractionwas extracted with 2 times 20 cm3 of dichloromethane
  5. washthe combined extracts were washed with 2 times 30 cm3 of water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  9. customAn oil was obtained
  10. customwhich oil was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 2.5 cm; silica volume 150 cm3), elution
  11. concentrationconcentrated as above
  12. customAn oil was obtained
  13. customthe hydrochloride of which was prepared in the following way
  14. customThe precipitate formed
  15. filtrationwas filtered off
  16. customdried in an oven under reduced pressure (10 Pa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-2d4b4c3b14cb411ead9b1fa291085138
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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