3-Butynoic Acid → HCID 16450136, compound

HRID 2208601Notes

Reaction equation

HRID 2208601 reaction equation
[C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][C:12]#[CH:13])[CH2:8][C:9]#[CH:10])([CH3:4])([CH3:3])[CH3:2].[C:15]([OH:20])(=[O:19])[CH2:16][C:17]#[CH:18]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh].C(O)C>[C:1]([O:5][C:6]([N:7]1[CH2:8][C:9]2[C:12](=[CH:13][CH:18]=[C:17]([CH2:16][C:15]([OH:20])=[O:19])[CH:10]=2)[CH2:11]1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 1375473-Butynoic AcidHCID 21250534HCID 21250534, compound

Product 1

HCID 16450136HCID 16450136, compound

Reagents, catalysts & solvents 2

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)CatalystHCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of di-prop-2-ynyl-carbamic acid tert-butyl ester (4.78 g, 24.7 mmol) and ethanol (120 mL) was prepared under argon and cooled to 0° C. for 15 min. 3-Butynoic acid (3.64 g, 43.3 mmol) and tris(triphenylphosphine)rhodium (I) chloride (1.14 g, 1.23 mmol) were added and reaction was gradually warmed to room temperature over 1.3 hr. The reaction was then heated to 45° C. for 17 hr. The reaction was cooled to room temperature and concentrated in vacuo. The residue was diluted with 1N NaOH and extracted with diethyl ether (3×). The aqueous layer was acidified to pH˜1 with 1N HCl and extracted with EtOAc (3×). The combined EtOAc layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (EtOAc:Hexane, 5-100%). ESI-MS m/z 278 (MH)+.

Workup

  1. customwas prepared under argon
  2. customreaction
  3. temperaturewas gradually warmed to room temperature over 1.3 hr
  4. temperatureThe reaction was then heated to 45° C. for 17 hr
  5. temperatureThe reaction was cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted with 1N NaOH
  8. extractionextracted with diethyl ether (3×)
  9. extractionextracted with EtOAc (3×)
  10. dry with materialThe combined EtOAc layers were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified by flash chromatography on silica gel (EtOAc:Hexane, 5-100%)

Sources & evidence

ORD record
ord-c9fee07b185c494b848331e4685a5ef3
Source dataset
uspto-grants-2016_06
Patent number
US09376454B2

Reaction notes

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