Water → HCID 67189162, compound

HRID 546229Notes

Reaction equation

HRID 546229 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][CH2:23][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:26].[K+].[OH2:31]>CO>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:16]([CH2:20][CH:21]2[CH2:22][CH2:23][CH2:24]2)[C:17]([OH:19])=[O:18])[CH:11]=[CH:12][C:13]=1[S:14]([CH3:15])(=[O:26])=[O:31]

Participants

6

Reactant 4

HCID 962Water3×HCID 516875Potassium PermanganateHCID 23667635Sodium periodate2×HCID 67192289HCID 67192289, compound

Product 1

HCID 67189162HCID 67189162, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

In a flask was placed sodium periodate (187 mg, 0.86 mmol) and water (1.5 mL). To this solution was then added dropwise (R)-2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclobutyl-propionic acid (132 mg, 0.46 mmol) in methanol (3.5 mL). The reaction was then stirred at 25° C. for 1 h after which time there was a white precipitate forming. Thin layer chromatography indicated the reaction was not complete so another portion of sodium periodate (120 mg, 0.5 mmol) in water (1 mL) was added and stirred another 1 h, the reaction was then stored at 4° C. for 16 h. The reaction was then filtered through a plug of celite and was concentrated in vacuo and then azeotroped with acetonitrile. The residue was then dissolved in methanol (6 mL) and added slowly to a solution of potassium permanganate (85 mg, 0.51 mmol) in water (1.5 mL) and stirred at 25° C. for 1 h. After this time the reaction was concentrated in vacuo and the residue was dissolved in acetonitrile and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes to 10% methanol/ethyl acetate) to afford (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclobutyl-propionic acid (95 mg, 65%) as a colorless gum: [α]30589=−42.0° (c=0.20, methylene chloride); ES-HRMS m/e calcd for C14H17O4SCl (M+Na)+ 339.0428, observed 339.0427; 1H NMR (300 MHz, DMSO-d6) δ 1.49-2.16 (m, 9H, CH and 4×CH2), 3.36 (s, 3H, SO2CH3), 3.60 (t, J=7.3 Hz, 1H, ArCHCO), 7.54 (dd, Jm=1.5 Hz, Jo=8.2 Hz, 1H, Ar), 7.67 (d, Jm=1.5 Hz, 1H, Ar), 7.99 (d, Jo=8.2 Hz, 1H, Ar), 12.71 (s, 1H, CO2H).

Workup

  1. customIn a flask was placed
  2. customforming
  3. additionwas added
  4. stirringstirred another 1 h
  5. waitthe reaction was then stored at 4° C. for 16 h
  6. filtrationThe reaction was then filtered through a plug of celite
  7. concentrationwas concentrated in vacuo
  8. customazeotroped with acetonitrile
  9. dissolutionThe residue was then dissolved in methanol (6 mL)
  10. stirringstirred at 25° C. for 1 h
  11. concentrationAfter this time the reaction was concentrated in vacuo
  12. dissolutionthe residue was dissolved in acetonitrile
  13. concentrationconcentrated with silica gel (2 g) in vacuo
  14. custompurified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes to 10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-10d5f0dc9e8743b5b93e851f387b0939
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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