Methanol → (3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)piperidine-3-carboxylate

HRID 393220Notes

Reaction equation

HRID 393220 reaction equation
[O:1]=[C:2]([C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][CH:22]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][C@@H:6]1[C:18](O)=[O:19].S(Cl)(Cl)=O.[CH3:37][OH:38]>>[O:1]=[C:2]([C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][CH:22]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][NH:8][CH2:7][C@@H:6]1[C:18]([O:38][CH3:37])=[O:19]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 53238172(3R,4R)-1-(tert-butoxycarbonyl)-4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)piperidine-3-carboxylic acid

Product 1

HCID 53238173(3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)piperidine-3-carboxylate

Conditions

Temperature
-30 °C

Procedure

A solution of 19.4 g of (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-(t-butyloxycarbonyl)piperidine-3-carboxylic acid (80% content) in 355 cm3 of methanol is cooled to a temperature in the region of −30° C. Thionyl chloride (7.7 cm3)is added with stirring while maintaining the temperature between −25 and −30° C. After the addition, the mixture is maintained in the vicinity of −30° C. for 30 minutes and then the temperature is allowed to return to the vicinity of 20° C. After stirring at ambient temperature for 19 hours, the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 30° C. The residue is taken up in 300 cm3 of water to which 200 cm3 of dichloromethane have been added, and then stirred. The organic phase is separated by settling; the aqueous phase is again extracted with 200 cm3 of dichloromethane. The aqueous solution is brought to pH 8 by gradual addition of solid sodium hydrogen carbonate. After extracting the alkaline solution 3 times with 200 cm3 of dichloromethane, the combined organic extracts are washed 2 times with 200 cm3 of water and then dried over magnesium sulfate. After filtering through a paper filter, the organic solution is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. to afford 4.51 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate.

Workup

  1. temperaturewhile maintaining the temperature between −25 and −30° C
  2. additionAfter the addition
  3. customto return to the vicinity of 20° C
  4. stirringAfter stirring at ambient temperature for 19 hours
  5. concentrationthe reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 30° C
  6. additionhave been added
  7. stirringstirred
  8. customThe organic phase is separated
  9. extractionthe aqueous phase is again extracted with 200 cm3 of dichloromethane
  10. additionThe aqueous solution is brought to pH 8 by gradual addition of solid sodium hydrogen carbonate
  11. extractionAfter extracting the alkaline solution 3 times with 200 cm3 of dichloromethane
  12. washthe combined organic extracts are washed 2 times with 200 cm3 of water
  13. dry with materialdried over magnesium sulfate
  14. filtrationAfter filtering through a paper
  15. filtrationfilter
  16. concentrationthe organic solution is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C.

Sources & evidence

ORD record
ord-a25d4843cc8846eca42a7c0471ac4d3b
Source dataset
uspto-grants-2004_10
Patent number
US06806277B2

Reaction notes

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