Acetic Acid → HCID 58573370, compound

HRID 932262Notes

Reaction equation

HRID 932262 reaction equation
[CH2:1]([C@@:4]1(C)[CH2:9][C@H:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([Cl:16])[CH:15]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:31][CH3:32])[CH2:25][S:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:5]1=[O:33])C=C.[C:35]([OH:38])(=[O:37])[CH3:36].[Mn]([O-])(=O)(=O)=[O:40].[K+].[OH2:45]>O.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[C:27]([S:26]([CH2:25][C@@H:24]([N:6]1[C@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[C@@H:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([Cl:16])[CH:15]=2)[CH2:9][C@@:4]([CH2:36][C:35]([OH:38])=[O:37])([CH3:1])[C:5]1=[O:33])[CH2:31][CH3:32])(=[O:40])=[O:45])([CH3:28])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 516875Potassium PermanganateHCID 68000252HCID 68000252, compound

Product 1

HCID 58573370HCID 58573370, compound

Reagents, catalysts & solvents 2

HCID 16212273Tetrabutylammonium chloride hydrateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of (3S,5R,6S)-3-allyl-1-((S)-1-(tert-butylthio)butan-2-yl)-6-(4-chlorophenyl)-5-(5-chloropyridin-3-yl)-3-methylpiperidin-2-one (Example 401, Step A, 0.147 g, 0.283 mmol;) with acetic acid (0.972 mL, 16.98 mmol) and tetrabutylammonium chloride hydrate (8.37 mg, 0.028 mmol) in 4 ml of DCM was cooled in an ice bath. A solution of potassium permanganate (0.268 g, 1.698 mmol) in 3 mL of water was added. The purple solution was stirred while cooling with an ice bath and allowed to warm to room temperature over 2 hours. Aq. NaS2O3 solution was added along with additional DCM. After filtering the solution through filter paper the filtrate was partitioned and then the aq. layer was washed with DCM. The combined organics were dried over Na2SO4 and concentrated. The product was purified by silica gel chromatography followed by preparatory HPLC (Agilent column, EXTEND C18 PrepHT, 5 μM, 30×250 mm) eluting with a gradient of 20% MeCN/H2O/0.1% TFA to 80% MeCN/H2O/0.1% TFA over 25 minutes. The fractions containing the product were combined, frozen in a acetone/dry ice bath and the solvents were removed on a lyophilizer to provide the title compound as an off-white solid.

Workup

  1. temperaturewhile cooling with an ice bath
  2. filtrationAfter filtering the solution
  3. filtrationthrough filter paper the filtrate
  4. customwas partitioned
  5. washthe aq. layer was washed with DCM
  6. dry with materialThe combined organics were dried over Na2SO4
  7. concentrationconcentrated
  8. customThe product was purified by silica gel chromatography
  9. washeluting with a gradient of 20% MeCN/H2O/0.1% TFA to 80% MeCN/H2O/0.1% TFA over 25 minutes
  10. additionThe fractions containing the product
  11. temperaturefrozen in a acetone/dry ice bath
  12. customthe solvents were removed on a lyophilizer

Sources & evidence

ORD record
ord-7a5d80df675e4b69bee865f6837269c1
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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