Sulfuric Acid → HCID 67190550, compound

HRID 546231Notes

Reaction equation

HRID 546231 reaction equation
[CH:1]1([CH2:5][C@H:6]([C:21]2[CH:26]=[CH:25][C:24]([S:27][CH3:28])=[C:23]([CH3:29])[CH:22]=2)[C:7](N([C@H](C)[C@H](O)C2C=CC=CC=2)C)=[O:8])[CH2:4][CH2:3][CH2:2]1.S(=O)(=O)(O)[OH:31]>O1CCOCC1.O>[CH:1]1([CH2:5][C@H:6]([C:21]2[CH:26]=[CH:25][C:24]([S:27][CH3:28])=[C:23]([CH3:29])[CH:22]=2)[C:7]([OH:8])=[O:31])[CH2:2][CH2:3][CH2:4]1

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 67190965HCID 67190965, compound

Product 1

HCID 67190550HCID 67190550, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (R)-3-cyclobutyl-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-2-(3-methyl-4-methylsulfanyl-phenyl)-propionamide (300 mg, 0.73 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 methylene chloride and concentrated with silica gel (2 g) and purified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes) to afford (R)-3-cyclobutyl-2-(3-methyl-4-methylsulfanyl-phenyl)-propionic acid (148 mg, 77%): [α]30589=−48.3° (c=0.18, methylene chloride); EI-HRMS m/e calcd for C15H20O2S (M+) 264.1184, observed 264.1183; 1H NMR (300 MHz, DMSO-d6) δ 1.47-2.14 (m, 9H, CH and 4×CH2), 2.21 (s, 3H, ArCH3), 2.43 (s, 3H, SCH3), 3.30 (t, J=7.4 Hz, 1H, ArCHCO), 7.05-7.15 (m, 3H, Ar), 12.28 (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 methylene chloride
  5. concentrationconcentrated with silica gel (2 g)
  6. custompurified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ce8bc8a4cde648c0a6aa5f75c4f9d868
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

Loading…