Sulfuric Acid → HCID 67192966, compound

HRID 546241Notes

Reaction equation

HRID 546241 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:22]2[CH:27]=[CH:26][C:25]([S:28][CH:29]([CH3:31])[CH3:30])=[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]([CH3:31])[CH3:30])=[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 67189598HCID 67189598, compound

Product 1

HCID 67192966HCID 67192966, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (R)-3-cyclopentyl-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-2-(4-isopropylsulfanyl-phenyl)-N-methyl-propionamide (830 mg, 1.89 mmol) in dioxane (10 mL) was treated with a 9 N aqueous sulfuric acid solution (6.0 mL). The resulting solution was then heated at 110° C. for 16 h. The reaction was then cooled and diluted with water (100 mL) and extracted with a chloroform/methanol solution (3:2, 2×50 mL). The organics were concentrated and then the residue dissolved in acetonitrile and silica gel (4 g) was added and it was concentrated in vacuo and then purified on Biotage Flash chromatography system (40S column, silica gel, 60% ethyl acetate/hexanes) to afford (R)-3-cyclopentyl-2-(4-isopropylsulfanyl-phenyl)-propionic acid (479 mg, 87%) as a yellow viscous oil: [α]28589=−52.3° (c=0.22, methanol); ES-HRMS m/e calcd for C17H24O2S (M+Na)+ 315.1389, observed 315.1388; 1H NMR JT (300 MHz, DMSO-d6) δ 1.07 (m, 2H, CH2), 1.22 (d, J=6.6 Hz, 6H, 2×CH3), 1.37-1.78 (m, 8H, 4×CH2), 1.94 (m, 1H, CH), 3.45 (m, 1H, SCH), 3.49 (d, J=7.5 Hz, 1H, ArCHCO), 7.25 (d, J=8.4 Hz, 2H, Ar), 7.32 (d, J=8.4 Hz, 2H, Ar), 12.35 (br, 1H, CO2H).

Workup

  1. temperatureThe reaction was then cooled
  2. extractionextracted with a chloroform/methanol solution (3:2, 2×50 mL)
  3. concentrationThe organics were concentrated
  4. dissolutionthe residue dissolved in acetonitrile
  5. additionsilica gel (4 g) was added
  6. concentrationit was concentrated in vacuo
  7. custompurified on Biotage Flash chromatography system (40S column, silica gel, 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2c3310a71e1f4e34863416d5ac51eb70
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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