Hydrochloric Acid → Rpr260243

HRID 1767103Notes

Reaction equation

HRID 1767103 reaction equation
[O:1]=[C:2]([C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][CH:28]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:15]=2[F:22])[CH2:7][C@@H:6]1[C:23]([O:25]C)=[O:24].Cl.O.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[O:1]=[C:2]([C:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][CH:28]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:15]=2[F:22])[CH2:7][C@@H:6]1[C:23]([OH:25])=[O:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 516892Sodium BicarbonateHCID 86591490(3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)-1-(3-(2,3,5-trifluorophenyl)prop-2-ynyl)piperidine-3-carboxylate

Product 1

HCID 11466357Rpr260243Yield 59.9%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of 1 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylate in 10 cm3 of a 5N aqueous hydrochloric acid solution is stirred for 4 hours at a temperature in the region of 80° C. After cooling to a temperature in the region of 20° C., 10 cm3 of water, then 10 cm3 of chloroform, and then 1.9 g of powdered sodium hydrogen carbonate are added. The mixture is extracted with 3 times 10 cm3 of chloroform. The organic phases are pooled, dried over sodium sulfate, filtered, and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20–45μ; diameter 2.5 cm; 30 g), eluting with a mixture of dichloromethane-methanol (96/4 by volume) and collecting first a fraction of 150 cm3, and then fractions of 10 cm3. Fractions 5 to 22 are pooled, and then concentrated as above. 0.583 g of (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylic acid, in the form of a green-colored solid which melts at around 70° C., is obtained.

Workup

  1. extractionThe mixture is extracted with 3 times 10 cm3 of chloroform
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  5. customThe residue obtained
  6. customis purified by chromatography under a nitrogen pressure of 50 kPa
  7. washon a column of silica gel (particle size 20–45μ; diameter 2.5 cm; 30 g), eluting with a mixture of dichloromethane-methanol (96/4 by volume)
  8. customcollecting first a fraction of 150 cm3
  9. concentrationconcentrated as above

Sources & evidence

ORD record
ord-986c5ad82f75465fa7f5cd29eef9fb0f
Source dataset
uspto-grants-2007_06
Patent number
US07232834B2

Reaction notes

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