Hydrochloric Acid → HCID 9990026, compound

HRID 433833Notes

Reaction equation

HRID 433833 reaction equation
[CH:1](N(C(C)C)CC)([CH3:3])[CH3:2].[CH2:10]([Li])CCC.[C:15]1([CH2:21][C:22]([OH:24])=[O:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(Br)C#C.C1(C)C=CC=CC=1.Cl>O1CCCC1.C(OCC)(=O)C>[CH3:10][O:23][C:22](=[O:24])[CH:21]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:3][C:1]#[CH:2]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 999Phenylacetic AcidHCID 1140TolueneHCID 7842Propargyl bromideHCID 81531DiisopropylethylamineHCID 178418339Butyllithium

Product 1

HCID 9990026HCID 9990026, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Diisopropyl ethyl amine (5.9 mL, 42 mmol) was dissolved in tetrahydrofuran (30 mL). Butyllithium, 2.5 M in hexanes, (16.8 mL, 42 mmol) was added slowly at A solution of phenyl acetic acid (2.72 g, 20 mmol) in tetrahydrofuran (20 mL) was added slowly via a dropping funnel over 20 minutes. The reaction was stirred for 25 minutes. Propargyl bromide was added as an 80% weight solution in toluene (2.3 mL, 21.0 mmol). The reaction was stirred for 1.5 hours and 4N hydrochloric acid (15 mL) was added. The mixture was diluted with ethyl acetate (50 mL). The organic portion was concentrated in vacuo. The residue was dissolved in diethyl ether and extracted with water (3×) and 1 N hydrochloric acid (3×). The organic portion was dried over magnesium sulfate and the solvent removed in vacuo. The resulting yellow solid (1.7 g) was dissolved in methanol (50 mL) and cooled to 0C. Acetylchloride (2 mL) was added and the reaction was allowed to warm to room temperature. After the reaction stirred for 18 hours, the solvent was removed in vacuo. The residue was dissolved in diethyl ether. The solution was extracted with saturated sodium bicarbonate, water, and brine. The organic portion was dried over magnesium sulfate and the solvent removed in vacuo. The residue was chromatographed on silica gel with 10% ethyl acetate in hexanes to give the title compound as an oil (0.58 g, 15%)

Workup

  1. additionwas added slowly via a dropping funnel over 20 minutes
  2. stirringThe reaction was stirred for 1.5 hours
  3. concentrationThe organic portion was concentrated in vacuo
  4. dissolutionThe residue was dissolved in diethyl ether
  5. extractionextracted with water (3×) and 1 N hydrochloric acid (3×)
  6. dry with materialThe organic portion was dried over magnesium sulfate
  7. customthe solvent removed in vacuo
  8. dissolutionThe resulting yellow solid (1.7 g) was dissolved in methanol (50 mL)
  9. temperaturecooled to 0C
  10. additionAcetylchloride (2 mL) was added
  11. stirringAfter the reaction stirred for 18 hours
  12. customthe solvent was removed in vacuo
  13. dissolutionThe residue was dissolved in diethyl ether
  14. extractionThe solution was extracted with saturated sodium bicarbonate, water, and brine
  15. dry with materialThe organic portion was dried over magnesium sulfate
  16. customthe solvent removed in vacuo
  17. customThe residue was chromatographed on silica gel with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9019ff293edf4debb09d70d1139f9bd8
Source dataset
uspto-grants-2003_12
Patent number
US06668527B2

Reaction notes

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