Potassium Iodide → HCID 131724014, compound

HRID 2414975Notes

Reaction equation

HRID 2414975 reaction equation
Cl.Cl.[OH:3][CH:4]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][C:18]=1[F:29])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH:8]1[C:13]([O:15][CH3:16])=[O:14].Br[CH2:31][CH2:32][S:33][C:34]1[S:35][CH:36]=[CH:37][CH:38]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.CN(C=O)C.C(N(CC)CC)C>[OH:3][CH:4]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][C:18]=1[F:29])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([CH2:31][CH2:32][S:33][C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)[CH2:9][CH:8]1[C:13]([O:15][CH3:16])=[O:14]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 122011192-(2-Bromoethylthio)-thiopheneHCID 131724015HCID 131724015, compound

Product 1

HCID 131724014HCID 131724014, compoundYield 46.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
65 °C

Procedure

0.74-cm3 of triethylamine was added to a solution composed of 1.17 g of methyl (3RS, 4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate dihydrochloride in 20-cm3 of acetonitrile and 10 cm3 of DMF, followed by 638 mg of 2-(2-bromoethylthio)thiophene in 10 cm3 of acetonitrile, 1 g of potassium carbonate and 431 mg of potassium iodide. The mixture was stirred for 15 hours at a temperature in the region of 65° C. under an inert atmosphere. After cooling to about 20° C., the reaction mixture was filtered on sintered glass. The filtrate was taken up in 100-cm3 of acetonitrile and concentrated under reduced pressure (5 kPa). The residue was taken up in 200-cm3 of ethyl acetate and 100-cm3 of water. The organic phase was separated after settling out, washed with twice 75-cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45μ; diameter 2 cm; height 40 cm), eluting with a mixture of cyclohexane-ethyl acetate (25/75 by volume) and collecting 50-cm3 fractions. Fractions 6 to 8 were concentrated. 630 mg of methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-carboxylate were obtained in the form of a colorless oil.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. filtrationthe reaction mixture was filtered on sintered glass
  3. concentrationconcentrated under reduced pressure (5 kPa)
  4. customThe organic phase was separated
  5. washwashed with twice 75-cm3 of a saturated aqueous sodium chloride solution
  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. customThe residue obtained
  10. customwas purified by chromatography, under a nitrogen pressure of 50 kPa
  11. washon a column of silica gel (particle size 20-45μ; diameter 2 cm; height 40 cm), eluting with a mixture of cyclohexane-ethyl acetate (25/75 by volume)
  12. customcollecting 50-cm3 fractions
  13. concentrationFractions 6 to 8 were concentrated

Sources & evidence

ORD record
ord-28c0be5cbca744628677eaf09e360c40
Source dataset
uspto-grants-2004_11
Patent number
US06815547B2

Reaction notes

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