Sulfuric Acid → HCID 67192289, compound

HRID 546228Notes

Reaction equation

HRID 546228 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:10]([CH2:25][CH:26]2[CH2:29][CH2:28][CH2:27]2)[C:11](N([C@H](C)[C@H](O)C2C=CC=CC=2)C)=[O:12])[CH:5]=[CH:6][C:7]=1[S:8][CH3:9].S(=O)(=O)(O)[OH:31]>O1CCOCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:10]([CH2:25][CH:26]2[CH2:29][CH2:28][CH2:27]2)[C:11]([OH:12])=[O:31])[CH:5]=[CH:6][C:7]=1[S:8][CH3:9]

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 67188846HCID 67188846, compound

Product 1

HCID 67192289HCID 67192289, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (R)-2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclobutyl-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-propionamide (330 mg, 0.76 mmol) in dioxane (4 mL) was treated with a 9 N aqueous sulfuric acid solution (2 mL). The resulting solution was then heated at 110° C. for 16 h. The reaction was then cooled and diluted with water (75 mL) and extracted with a chloroform/methanol solution (3:2, 2×50 mL) and then concentrated. The resulting residue was then dissolved in acetonitrile and concentrated with silica gel (3 g) and purified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes) to afford (R)-2-(3-chloro-4-methylsulfanyl-phenyl)-3-cyclobutyl-propionic acid (154 mg, 71%) as a yellow viscous oil: [α]30589=−48.3° (c=0.18, methylene chloride); ES-HRMS m/e calcd for C14H17O2SCl (M+Na)+ 307.0530, observed 307.0530; 1H NMR (300 MHz, DMSO-d6) δ 1.47-2.16 (m, 9H, CH and 4×CH2), 2.47 (s, 3H, SCH3), 3.40 (t, J=7.3 Hz, 1H, ArCHCO), 7.25 (s, 2H, Ar), 7.34 (s, 1H, Ar), 12.41 (s, 1H, CO2H).

Workup

  1. temperatureThe reaction was then cooled
  2. extractionextracted with a chloroform/methanol solution (3:2, 2×50 mL)
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was then dissolved in acetonitrile
  5. concentrationconcentrated with silica gel (3 g)
  6. custompurified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-90318b547ee94faca639a4e3244aa6c9
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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