(Diethylamino)sulfur trifluoride → HCID 22470318, compound

HRID 395013Notes

Reaction equation

HRID 395013 reaction equation
C(N(S(F)(F)[F:7])CC)C.[Cl:10][C:11]1[CH:12]=[N:13][C:14]2[C:19]([C:20]=1[CH:21](O)[CH2:22][CH2:23][C:24]1([C:41]([O:43][CH3:44])=[O:42])[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][O:32][C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[F:40])[CH2:26][CH2:25]1)=[CH:18][C:17]([O:46][CH3:47])=[CH:16][CH:15]=2.C(=O)([O-])O.[Na+]>ClCCl>[Cl:10][C:11]1[CH:12]=[N:13][C:14]2[C:19]([C:20]=1[CH:21]([F:7])[CH2:22][CH2:23][C:24]1([C:41]([O:43][CH3:44])=[O:42])[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][O:32][C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[F:40])[CH2:28][CH2:29]1)=[CH:18][C:17]([O:46][CH3:47])=[CH:16][CH:15]=2

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 22468978HCID 22468978, compound

Product 1

HCID 22470318HCID 22470318, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
3 °C

Procedure

0.2 cm3 of diethylaminosulfur trifluoride was added to a solution of 0.5 g of methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-hydroxypropyl]-1-[2-(2,5-difluorophenoxy)ethyl]piperidine-4-carboxylate in 20 cm3 of dichloromethane, with stirring and under an inert atmosphere, at a temperature in the region of 3° C. After stirring for 7 hours at a temperature in the region of 20° C., saturated sodium hydrogencarbonate solution was added to the reaction mixture. The aqueous phase was extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; diameter 1.5 cm; mass: 15 g), eluting with a mixture of ethyl acetate/petroleum ether (40-60° C.) (8/2 by volume). Fractions 9 to 11 were combined and then concentrated to dryness under the above conditions. 0.21 g of methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-fluoropropyl]-1-[2-(2,5-difluorophenoxy)ethyl]piperidine-4-carboxylate was obtained in the form of a thick yellow oil.

Workup

  1. additionwas added to the reaction mixture
  2. extractionThe aqueous phase was extracted with dichloromethane
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  6. customThe residue obtained
  7. customwas purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; diameter 1.5 cm; mass: 15 g)
  8. washeluting with a mixture of ethyl acetate/petroleum ether (40-60° C.) (8/2 by volume)
  9. concentrationconcentrated to dryness under the above conditions

Sources & evidence

ORD record
ord-af282614ac18440580de1ae575ffdaec
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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