Triethylamine → HCID 53674139, compound

HRID 52269Notes

Reaction equation

HRID 52269 reaction equation
[C:1]([N:5]([C@@H:9]1[CH2:14][C:13]2[C:15](OS(C(F)(F)F)(=O)=O)=[CH:16][CH:17]=[C:18]([F:19])[C:12]=2[O:11][CH2:10]1)[CH2:6][CH2:7][CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CN([CH:38]=[O:39])C.[CH3:40][OH:41]>>[C:1]([N:5]([C@@H:9]1[CH2:14][C:13]2=[C:15]([C:40]([O:39][CH3:38])=[O:41])[CH:16]=[CH:17][C:18]([F:19])=[C:12]2[O:11][CH2:10]1)[CH2:6][CH2:7][CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 21901440N,N-dimethylformamide methanolHCID 22871223(R)-3-(N-tert-Butyl-N-n-propylamino)-8-fluoro-5-trifluoromethylsulfonyloxy-3,4-dihydro-2H-1-benzopyran

Product 1

HCID 53674139HCID 53674139, compoundYield 89%

Conditions

Temperature
70 °C

Procedure

(R)-3-(N-tert-Butyl-N-n-propylamino)-8-fluoro-5-trifluoromethylsulfonyloxy-3,4-dihydro-2H-1-benzopyran (1.4 g, 3.3 mmol) and triethylamine (1.0 mL, 7.4 mmol) were dissolved in a solution of DMF/MeOH (6:2; 30 mL) and then degassed followed by the inlet of carbon monoxide (4×). With a slight positive pressure of carbon monoxide, palladium(II)-acetate (0.030 g) and 1,3-bis(diphenylphosphino)propane (0.060 g) were added and the reaction mixture was degassed and subjected to carbon monoxide once again. The reaction was heated to 70° C. (oil-bath temperature) under carbon monoxide atmosphere with vigorous stirring for 12 h. GC indicating an incomplete reaction (68% product vs. 21% starting material), the solution was cooled and then filtered through Celite. More palladium(II)-acetate (0.030 g) and 1,3-bis(diphenylphosphino)propane (0.060 g) were added and the reaction was resumed as described above. After another 3 h GC indicated a slight improvement of the ratio (77% vs. 12%) and the reaction was allowed to cool. The following day the solvent was removed in vacuo. The remaining red-brown oil was taken into saturated aqueous NaHCO3 and then extracted with EtOAc (3×50 mL). The combined organic phases were washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give the crude ester. Flash chromatography on silica [eluent: EtOAc (15 and 30%) in hexane] gave 0.178 g of starting material and 0.842 g (89% yield based on recovered starting material) of the title compound as a clear oil. [α]21D =-121.1° (C=0.9; CHCl3). GC-MS (70 eV) M=323 (14%).

Workup

  1. customdegassed
  2. additionWith a slight positive pressure of carbon monoxide, palladium(II)-acetate (0.030 g) and 1,3-bis(diphenylphosphino)propane (0.060 g) were added
  3. customthe reaction mixture was degassed
  4. customan incomplete reaction (68% product vs. 21% starting material)
  5. temperaturethe solution was cooled
  6. filtrationfiltered through Celite
  7. additionMore palladium(II)-acetate (0.030 g) and 1,3-bis(diphenylphosphino)propane (0.060 g) were added
  8. waitAfter another 3 h GC indicated
  9. temperatureto cool
  10. customThe following day the solvent was removed in vacuo
  11. extractionextracted with EtOAc (3×50 mL)
  12. washThe combined organic phases were washed with brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customto give the crude ester
  17. customFlash chromatography on silica [eluent: EtOAc (15 and 30%) in hexane] gave
  18. custom0.178 g of starting material and 0.842 g (89% yield based on recovered starting material) of the title compound as a clear oil
  19. custom[α]21D =-121.1° (C=0.9; CHCl3)

Sources & evidence

ORD record
ord-d1ac541f30ec461f83d846f8cccd3190
Source dataset
uspto-grants-1997_04
Patent number
US05616610

Reaction notes

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