Oxygen → HCID 22597961, compound

HRID 1760227Notes

Reaction equation

HRID 1760227 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][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]1[C:28]([OH:30])=[O:29])=[CH:9][C:8]([O:31][CH3:32])=[CH:7][CH:6]=2.O=O.CC(C)([O-:38])C.[K+].C(OC)(=O)C>CS(C)=O.C(O)(C)(C)C.O.C(O)(=O)C>[OH:38][CH:12]([C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:31][CH3:32])[CH:9]=2)[N:4]=[CH:3][C:2]=1[Cl:1])[CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[CH2:17][CH:16]1[C:28]([OH:30])=[O:29]

Participants

9

Reactant 4

HCID 977Oxygen2×HCID 6584Methyl AcetateHCID 22597936HCID 22597936, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 22597961HCID 22597961, compoundYield 88.5%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
0 °C

Procedure

100 cm3 of tert-butanol are added to 5.55 g of (3RS,4RS)-4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)piperidine-3-carboxylic acid in 450 cm3 of dimethyl sulfoxide, and the reaction mixture is then saturated with oxygen for 30 minutes. A solution of 3.36 g of potassium tert-butoxide in 40 cm3 of tert-butanol is then added over 40 minutes. The mixture is allowed to stir for 2 hours while maintaining the oxygen flow rate, and then the medium is cooled to around 0° C. in order to add 1.8 cm3 of acetic acid in 30 cm3 of distilled water. 1000 cm3 of distilled water and 1000 cm3 of methyl acetate are then poured onto the reaction medium. The organic phase is then washed with 8 times 250 cm3 of distilled water then with 2 times 100 cm3 of sodium chloride. The pooled aqueous phases are re-extracted with 500 cm3 of ethyl acetate. The two organic phases are pooled and then dried over magnesium sulfate for 1 hour. Filtration is carried out through a sintered glass funnel, followed by concentration under reduced pressure (2 kPa; 45° C.). The residue is taken up in 250 cm3 of methyl acetate and 100 cm3 of distilled water. The organic phase is washed with 3 times 50 cm3 of distilled water and then with 50 cm3 of a saturated aqueous sodium chloride solution. Drying is carried out over magnesium sulfate for 1 hour, filtration is carried out through a sintered glass funnel, and then evaporation is carried out under reduced pressure (2 kPa; 45° C.). 5.08 g of (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(tert-butyloxy-carbonyl)piperidine-3-carboxylic acid are obtained.

Workup

  1. washThe organic phase is then washed with 8 times 250 cm3 of distilled water
  2. extractionThe pooled aqueous phases are re-extracted with 500 cm3 of ethyl acetate
  3. dry with materialdried over magnesium sulfate for 1 hour
  4. filtrationFiltration
  5. customis carried out through a sintered glass funnel
  6. concentrationfollowed by concentration under reduced pressure (2 kPa; 45° C.)
  7. washThe organic phase is washed with 3 times 50 cm3 of distilled water
  8. customDrying
  9. waitis carried out over magnesium sulfate for 1 hour
  10. filtrationfiltration
  11. customis carried out through a sintered glass funnel
  12. customevaporation
  13. customis carried out under reduced pressure (2 kPa; 45° C.)

Sources & evidence

ORD record
ord-a27d035b0c124c66a63138d167b6a58d
Source dataset
uspto-grants-2005_01
Patent number
US06841562B2

Reaction notes

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