Sulfuric Acid → HCID 67189705, compound

HRID 546213Notes

Reaction equation

HRID 546213 reaction equation
CC1(C)C[O:36][C:5]2([CH2:9][C@@H:8]([CH2:10][C@H:11]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[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:40]>O1CCOCC1.O>[O:36]=[C:5]1[CH2:6][CH2:7][C@H:8]([CH2:10][C@H:11]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)[C:12]([OH:40])=[O:13])[CH2:9]1

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 67187930HCID 67187930, compound

Product 1

HCID 67189705HCID 67189705, compoundYield 73%

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-trifluoromethyl-phenyl)-propionamide (250 mg, 0.47 mmol) in dioxane (2.5 mL) was treated with a 9 N aqueous sulfuric acid solution (1.5 mL). The resulting solution was then heated at 110° C. for 16 h. The reaction was then cooled and diluted with water (50 mL) and extracted with a chloroform/methanol solution (3:2, 2×25 mL) and then concentrated. The resulting residue was then dissolved in acetonitrile and concentrated with silica gel (2 g) and purified on Biotage Flash chromatography system (40S column, silica gel, 60% ethyl acetate/hexanes) to afford (R)-3-((R)-3-oxo-cyclopentyl)-2-(3-trifluoromethyl-phenyl)-propionic acid (102 mg, 73%) as a pale yellow oil: [α]22589=−86.1° (c=0.18, methanol); ES-HRMS m/e calcd for C15H15O3F3 (M+Na)+ 323.0865, observed 323.0865; 1H NMR (400 MHz, CDCl3) δ 1.55 (m, 1H, CH), 1.82-2.47 (m, 8H, 4×CH2), 3.73 (t, J=7.8 Hz, 1H, ArCHCO), 7.47-7.61 (m, 4H, Ar).

Workup

  1. temperatureThe reaction was then cooled
  2. extractionextracted with a chloroform/methanol solution (3:2, 2×25 mL)
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was then dissolved in acetonitrile
  5. concentrationconcentrated with silica gel (2 g)
  6. custompurified on Biotage Flash chromatography system (40S column, silica gel, 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f5a669e5e3ee47a29fa8060ce159d0a3
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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