Sulfuric Acid → HCID 67189647, compound

HRID 546219Notes

Reaction equation

HRID 546219 reaction equation
CC1(C)C[O:35][C:5]2([CH2:9][C@@H:8]([CH2:10][C@H:11]([C:26]3[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[C:28]([CH3:34])[CH:27]=3)[C:12](N([C@H](C)[C@H](O)C3C=CC=CC=3)C)=[O:13])[CH2:7][CH2:6]2)OC1.S(=O)(=O)(O)[OH:39]>O1CCOCC1.O>[CH3:34][C:28]1[CH:27]=[C:26]([C@@H:11]([CH2:10][C@H:8]2[CH2:7][CH2:6][C:5](=[O:35])[CH2:9]2)[C:12]([OH:39])=[O:13])[CH:31]=[CH:30][C:29]=1[S:32][CH3:33]

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 67190821HCID 67190821, compound

Product 1

HCID 67189647HCID 67189647, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (R)-3-((R)-8,8-dimethyl-6,10-dioxa-spiro[4.5]dec-2-yl)-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-2-(3-methyl-4-methylsulfanyl-phenyl)-propionamide (1.35 g, 2.57 mmol) in dioxane (14 mL) was treated with a 9 N aqueous sulfuric acid solution (8 mL). The resulting solution was then heated at 110° C. for 16 h. The reaction was then cooled and diluted with water (150 mL) and extracted with a chloroform/methanol solution (3:2, 2×50 mL) and then combined the organic extracts and concentrated. The resulting residue was then dissolved in acetonitrile and concentrated with silica gel (3 g) and purified on Biotage Flash chromatography system (40 L column, silica gel, 60% ethyl acetate/hexanes) to afford (R)-2-(3-methyl-4-methylsulfanyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionic acid (674 mg, 90%) as a pale yellow gum: [α]28958−115.4° (c=0.35, methanol); ES-HRMS m/e calcd for C16H20O3S (M+Na)+ 315.1025, observed 315.1025; 1H NMR (300 MHz, DMSO-d6) δ 1.46 (m, 1H, CH), 1.76-2.32 (m, 8H, 4×CH2), 2.22 (s, 3H, ArCH3), 2.44 (s, 3H, SCH3), 3.48 (m, 1H, ArCHCO), 7.14 (m, 3H, Ar), 12.31 (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 (40 L column, silica gel, 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d78a91a9e87743d68a3f86ff168f7f94
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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