Ethyl propiolate → HCID 57264429, compound

HRID 1420804Notes

Reaction equation

HRID 1420804 reaction equation
C([Li])CCC.[C:6]([O:10][CH2:11][CH3:12])(=[O:9])[C:7]#[CH:8].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C:22](=[O:26])[C@@H:21]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])O.[Na+]>O1CCCC1.C(O)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C@:22]([C:8]#[C:7][C:6]([O:10][CH2:11][CH3:12])=[O:9])([OH:26])[C@@H:21]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 12182Ethyl propiolateHCID 516892Sodium BicarbonateHCID 10956740(2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-oneHCID 178418339Butyllithium

Product 1

HCID 57264429HCID 57264429, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (2.28 ml, 1.6M solution in hexanes, 3.64 mmol) was added slowly to a cooled (-78° C.) solution of ethyl propiolate (0.370 ml, 3.64 mmol) in tetrahydrofuran (10 ml). the soluton was stirred for 10 min. at -78° C. after addition was complete then (2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-one (Description 1, 1,0 g, 3.64 mmol) in tetrahydrofuran (10 ml) was added, the temperature being maintained below -75° C. The mixture was stirred for a further 10 min, then warmed to -60° C. when glacial acetic acid (1 ml) was added. The mixture was warmed to room temperature and poured into saturated aqueous sodium hydrogen carbonate (20 ml). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (20 ml). The combined organic fractions were dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (90:10), to give the title compound as a gum (801 mg, 59%), 1H NMR (250 MHz, CDCl3) δ7.50 (2H, m), 7.35 (3H, m), 5.49 (1H, s), 4.25 (2H, q, J 7.12 Hz), 4.15 (1H, m), 3.02 (1H, m), 2.23 (2H, m), 2.00 (2H, m), 1.78 (1H, m), 1.37 (9H, s), and 1.29 (3H, t, J 7.12 Hz), m/z (ES+) 374 (M+1).

Workup

  1. additionafter addition
  2. temperaturethe temperature being maintained below -75° C
  3. stirringThe mixture was stirred for a further 10 min
  4. additionwas added
  5. temperatureThe mixture was warmed to room temperature
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with ethyl acetate (20 ml)
  8. dry with materialThe combined organic fractions were dried (Na2SO4)
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by flash column chromatography on silica gel
  11. washeluting with hexane/EtOAc (90:10)

Sources & evidence

ORD record
ord-6bac4eebe9f842748744177dd307b1b5
Source dataset
uspto-grants-2000_06
Patent number
US06071927

Reaction notes

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