Water → Tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-methanesulfonyloxymethylpiperidine-1-carboxylate

HRID 394993Notes

Reaction equation

HRID 394993 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([CH2:28][OH:29])[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[CH:9][C:8]([O:30][CH3:31])=[CH:7][CH:6]=2.[CH3:32][S:33](Cl)(=[O:35])=[O:34].O>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([CH2:28][O:29][S:33]([CH3:32])(=[O:35])=[O:34])[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:19][CH2:20]1)=[CH:9][C:8]([O:30][CH3:31])=[CH:7][CH:6]=2

Participants

6

Reactant 3

HCID 962Water2×HCID 31297Methanesulfonyl chlorideHCID 22468565Tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-hydroxymethylpiperidine-1-carboxylate

Product 1

HCID 22469120Tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-methanesulfonyloxymethylpiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 24.8 g of tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-hydroxymethylpiperidine-1-carboxylate in 400 cm3 of dichloromethane and 12.9 cm3 of triethylamine was cooled to about 0° C. with stirring and under an inert atmosphere. Methanesulfonyl chloride, dissolved beforehand in 125 cm3 of dichloromethane, was added dropwise and the reaction mixture was then stirred for 18 hours at a temperature in the region of 20° C. 200 cm3 of water were added to the reaction mass, followed by a further addition of 3 000 cm3 of water. The phases were separated by settling and the aqueous phase was extracted with 200 cm3 of dichloromethane. The organic extracts were washed with 300 cm3 of aqueous sodium chloride solution, dried over sodium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 45° C. 30.6 g of tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-methanesulfonyloxymethylpiperidine-1-carboxylate were obtained in the form of an orange-colored oil.

Workup

  1. additionwas added dropwise
  2. stirringthe reaction mixture was then stirred for 18 hours at a temperature in the region of 20° C
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with 200 cm3 of dichloromethane
  5. washThe organic extracts were washed with 300 cm3 of aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 45° C

Sources & evidence

ORD record
ord-0db9bb0c68294892b678e26b74bb4552
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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