Ammonia → HCID 53700235, compound

HRID 1780053Notes

Reaction equation

HRID 1780053 reaction equation
[NH2-].[Li+].N.[CH2:4]([O:7][CH:8]([O:10][CH2:11][CH3:12])[CH3:9])[C:5]#[CH:6].[C:13]([O:16][C:17](=[O:19])[CH3:18])(=O)[CH3:14].[C:20](=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CS(C)=O>[C:17]([O:16][C@H:13]([CH3:20])[CH2:14][C:6]#[C:5][CH2:4][O:7][CH:8]([O:10][CH2:11][CH3:12])[CH3:9])(=[O:19])[CH3:18]

Participants

9

Reactant 5

HCID 222AmmoniaHCID 7918Acetic AnhydrideHCID 24532Lithium amideHCID 867741-Propyne, 3-(1-ethoxyethoxy)-HCID 516892Sodium Bicarbonate2×

Product 1

HCID 53700235HCID 53700235, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A second variation was initiated by adding DMSO (1000 ml) to 95% lithium amide (87.1 g, 3.60 mole) at 20° C. over 10 minutes without an exothermie reaction, heated to 60° C. over 30 minutes and maintained at that temperature for 30 minutes when ammonia evolution had ceased. The mixture was cooled to 15° C. over 20 minutes and acetaldehyde ethyl propargyl acetal (580 ml, 3.50 mole) was added to the resulting slurry over 40 minutes with cooling in an ice bath and maintaining the temperature at 15° C. The reaction mixture was stirred for 20 minutes while cooling to 2° C., and chiral R-(+)-propylene oxide (252 ml, 3.60 mole) was added over 120 minutes with ice bath cooling. The temperature was increased to 20° C. The reaction was maintained at 20° C. for 120 minutes and an aliquot removed was shown to be 94.6% 5-(R)-hydroxy-1-ethoxyethoxy-2-hexyne by GC-MS. Acetic anhydride (570 ml, 6.0 mole) was added over 45 minutes with ice bath cooling and the temperature increased to 30° C. The reaction was stirred at 60° C. for 16 hours. Saturated sodium bicarbonate (500 ml) was added, followed by solid sodium bicarbonate (700 g, 8.3 mole) in 50 g portions. Water (1000 ml) and ethyl acetate (1000 ml) were added, the phases separated and the ethyl acetate phase was washed with 25% saturated sodium chloride solution (2×800 ml). The solvent was removed to afford a residue of crude 5-(R)-acetoxy-1-ethoxyethoxy-2-hexyne (680 g, 85% yield).

Workup

  1. customwithout an exothermie reaction
  2. temperatureThe mixture was cooled to 15° C. over 20 minutes
  3. temperaturewith cooling in an ice bath
  4. temperaturemaintaining the temperature at 15° C
  5. temperaturewhile cooling to 2° C.
  6. temperaturecooling
  7. temperatureThe temperature was increased to 20° C
  8. temperatureThe reaction was maintained at 20° C. for 120 minutes
  9. customan aliquot removed
  10. temperaturecooling
  11. temperaturethe temperature increased to 30° C
  12. stirringThe reaction was stirred at 60° C. for 16 hours
  13. customthe phases separated
  14. washthe ethyl acetate phase was washed with 25% saturated sodium chloride solution (2×800 ml)
  15. customThe solvent was removed

Sources & evidence

ORD record
ord-e07296db73364a9692811a3f5da829eb
Source dataset
uspto-grants-1997_05
Patent number
US05629423

Reaction notes

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