Ammonium Chloride → HCID 131723281, compound

HRID 2186378Notes

Reaction equation

HRID 2186378 reaction equation
[O:1]=[C:2]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][CH:25]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:7][C@@H:6]1[C:20]([O:22][CH3:23])=[O:21].[BH4-].[Na+].[Cl-].[NH4+]>CO.ClCCl.CO>[OH:1][CH:2]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][CH:25]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:7][C@@H:6]1[C:20]([O:22][CH3:23])=[O:21]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 86758161HCID 86758161, compound

Product 1

HCID 131723281HCID 131723281, compoundYield 42.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A stirred solution of 0.77 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(pyridin-2-ylthio)ethyl]piperidine-3-carboxylate in 15 cm3 of methanol was cooled to a temperature in the region of 0° C. under an inert atmosphere. 0.063 g of sodium borohydride was added and then, after 15 minutes, the temperature was brought back to the region of 20° C. for 16 hours. After adding 5 cm3 of a saturated aqueous ammonium chloride solution, the mixture was stirred for 10 minutes and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in 10 cm3 of a dichloromethane/methanol (95/5 by volume) mixture and then filtered. The insoluble material was washed with 2 times 5 cm3 of the same mixture. The filtrate was evaporated under the same conditions as above. A foam was obtained, which product was purified by chromatography under a nitrogen pressure of 100 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; silica height 35 cm), elution was carried out first with a dichloromethane/methanol (96/4 by volume) mixture, and 35-cm3 fractions were collected. After the first 50 fractions, elution was carried out with a dichloromethane/methanol (90/10 by volume) mixture. Fractions 61 to 90 were combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.33 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(pyridin-2-ylthio)ethyl]piperidine-3-carboxylate was obtained in the form of a lacquer with a beige color.

Workup

  1. waitthe temperature was brought back to the region of 20° C. for 16 hours
  2. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. filtrationfiltered
  5. washThe insoluble material was washed with 2 times 5 cm3 of the same mixture
  6. customThe filtrate was evaporated under the same conditions as above
  7. customA foam was obtained
  8. customwhich product was purified by chromatography under a nitrogen pressure of 100 kPa
  9. washon a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; silica height 35 cm), elution
  10. customwere collected
  11. washAfter the first 50 fractions, elution
  12. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-8d1137d4a31f4396a3cc0247ba6f3be8
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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