Water → HCID 67191351, compound

HRID 546180Notes

Reaction equation

HRID 546180 reaction equation
I([O-])(=O)(=O)=O.[Na+].[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:16]([CH2:20][CH:21]2[CH2:24][C:23](=[O:25])[CH2:22]2)[C:17]([OH:19])=[O:18])[CH:11]=[CH:12][C:13]=1[S:14][CH3:15].[Mn]([O-])(=O)(=O)=[O:27].[K+].[OH2:32]>CO>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:16]([CH2:20][CH:21]2[CH2:22][C:23](=[O:25])[CH2:24]2)[C:17]([OH:19])=[O:18])[CH:11]=[CH:12][C:13]=1[S:14]([CH3:15])(=[O:27])=[O:32]

Participants

6

Reactant 4

HCID 962Water3×HCID 516875Potassium Permanganate2×HCID 23667635Sodium periodateHCID 671903062(R)-(3-chloro-4-methylsulfanyl-phenyl)-3-(3-oxo-cyclobutyl)-propionic acid

Product 1

HCID 67191351HCID 67191351, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
25 °C

Procedure

In a round bottom flask was placed sodium periodate (0.29 g, 1.36 mmol) in water (1.0 ml). To this was added a solution of 2(R)-(3-chloro-4-methylsulfanyl-phenyl)-3-(3-oxo-cyclobutyl)-propionic acid (prepared as in Example 93, 0.22 g, 0.74 mmol) in methanol (3 ml) and the reaction was stirred at 25° C. for 6 h. After this time, the solids were filtered off and the filtrate was concentrated in vacuo and azeotroped with acetonitrile (2×10 ml). The resulted in an off-white solid that was then dissolved in methanol (4 ml) and to this was added potassium permanganate (0.17 g, 1.07 mmol) in water (2 ml) and stirred at 25° C. for 5 h. After this time, there was still starting material present by HPLC so another portion of potassium permanganate (80 mg, 0.51 mmol) in water (1 ml) and it was stirred overnight. The reaction still showed starting material was not consumed but it was worked up anyway. The reaction was filtered through celite and washed with a solution of methanol/methylene chloride (1:1). The organics were concentrated in vacuo and azeotroped with acetonitrile (3×10 ml). Purification on an AnaLogix Intelliflash system (40 g column, 3% methanol/methylene chloride+1% acetic acid) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclobutyl)-propionic acid (65 mg, 27%) as a white gummy solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.93-2.32 (m, 3H, CH and CH2), 2.63-2.80 (m, 2H, 2×CH or 2×CH2), 2.90-3.13 (m, 2H, 2×CH or 2×CH2), 3.35 (s, 3H, SO2CH3), 3.72 (t, J=7.6 Hz, 1H, ArCHCO2), 7.58 (dd, Jm=1.6 Hz, Jo=8.2 Hz, 1H, Ar), 7.72 (d, Jm=1.6 Hz, 1H, Ar), 8.02 (d, Jo=8.2 Hz, 1 H, Ar), 12.81 (brs, 1H, CO2H).

Workup

  1. customIn a round bottom flask was placed
  2. filtrationAfter this time, the solids were filtered off
  3. concentrationthe filtrate was concentrated in vacuo
  4. customazeotroped with acetonitrile (2×10 ml)
  5. customThe resulted in an off-white solid
  6. stirringstirred at 25° C. for 5 h
  7. stirringwas stirred overnight
  8. customThe reaction
  9. customwas not consumed
  10. filtrationThe reaction was filtered through celite
  11. washwashed with a solution of methanol/methylene chloride (1:1)
  12. concentrationThe organics were concentrated in vacuo
  13. customazeotroped with acetonitrile (3×10 ml)
  14. customPurification on an AnaLogix Intelliflash system (40 g column, 3% methanol/methylene chloride+1% acetic acid)

Sources & evidence

ORD record
ord-3c8a8ca2f51e41b296dfe3f481825b4c
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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