Sulfuric Acid → (R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-propionic acid

HRID 546237Notes

Reaction equation

HRID 546237 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:22]2[CH:27]=[CH:26][C:25]([S:28][CH:29]3[CH2:31][CH2:30]3)=[CH:24][CH:23]=2)[C:8](N([C@H](C)[C@H](O)C2C=CC=CC=2)C)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.S(=O)(=O)(O)[OH:33]>O1CCOCC1.O>[CH:1]1([CH2:6][C@H:7]([C:22]2[CH:27]=[CH:26][C:25]([S:28][CH:29]3[CH2:31][CH2:30]3)=[CH:24][CH:23]=2)[C:8]([OH:9])=[O:33])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 67188487HCID 67188487, compound

Product 1

HCID 67188934(R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-propionic acidYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A solution of (R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-propionamide (715 mg, 1.63 mmol) in dioxane (5 mL) was treated with a 9 N aqueous sulfuric acid solution (1.3 mL). The resulting solution was then heated at 105° C. for 16 h. The reaction was then cooled and diluted with water (13 mL) and extracted with a chloroform/methanol solution (3:2, 3×20 mL) and then combined the organic extracts dried over magnesium sulfate, filtered and concentrated. Purification on an AnaLogix Intelliflash system (12 g column, 10% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded (R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-propionic acid (278 mg, 59%) as a white solid: [α]25589=−52.6° (c=0.19, methanol); ES-HRMS m/e calcd for C17H22O2S (M−H)− 289.1268, observed 289.1268; 1H NMR (300 MHz, CDCl3) δ 1.61-2.05 (m, 4H, 2×CH2), 2.45 (s, 3 H, ArCH3), 3.76 (m, 2H, OCH2), 4.00 (m, 2H, SO3CH2), 4.08 (m, 1H, OCH), 7.35 (brd, 2H, Ar), 7.81 (brd, 2H, Ar).

Workup

  1. temperatureThe reaction was then cooled
  2. extractionextracted with a chloroform/methanol solution (3:2, 3×20 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification on an AnaLogix Intelliflash system (12 g column, 10% ethyl acetate/hexanes to 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c3912700438744aeb37ecbabdc7ef160
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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