Triethylamine → Methyl (R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxylate

HRID 52278Notes

Reaction equation

HRID 52278 reaction equation
[CH:1]1([N:5]([C@@H:9]2[CH2:14][C:13]3[C:15](OS(C(F)(F)F)(=O)=O)=[CH:16][CH:17]=[C:18]([F:19])[C:12]=3[O:11][CH2:10]2)[CH:6]([CH3:8])[CH3:7])[CH2:4][CH2:3][CH2:2]1.[C]=O.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CN([CH:69]=[O:70])C.[CH3:71][OH:72]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]1([N:5]([C@@H:9]2[CH2:14][C:13]3=[C:15]([C:71]([O:70][CH3:69])=[O:72])[CH:16]=[CH:17][C:18]([F:19])=[C:12]3[O:11][CH2:10]2)[CH:6]([CH3:8])[CH3:7])[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 21901440N,N-dimethylformamide methanolHCID 54082177(R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-5-trifluoromethylsulfonyloxy-3,4-dihydro-2H-1-benzopyranHCID 178418416HCID 178418416, compound

Product 1

HCID 53695439Methyl (R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

(R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-5-trifluoromethylsulfonyloxy-3,4-dihydro-2H-1-benzopyran (1.65 g, 4.01 mmol) was dissolved in a solution of DMF/methanol (6:2, 30 mL) and then degassed followed by the inlet of carbonmonoxide (×3). With a slight positive pressure of carbonmonoxide, palladium(II)-acetate (30 mg), 1,3-bis(diphenylphosphino)propane (55 mg) and triethylamine (1.25 mL, 8.8 mmol) were added and the reaction mixture was degassed and subjected to carbonmonoxide once again. The reaction was heated to 70° C. under carbonmonoxide atmosphere with vigorous stirring for 6 h. The reaction was allowed to cool and the solvent was ether. The combined ether portions were dried (MgSO4), removed in vacuo. The remains were taken into a 2M solution of NH3 and then extracted, twice, with diethyl filtered, and the solvent removed in vacuo to give the crude residue. Chromatography on silica (eluent: 8% ethyl acetate/hexane) gave 1.18 mg (92% yield) of the title compound as a clear oil. [α]21D =-139.1° (C=0.1; CHCl3) GC-MS (70 eV) M=321 (3%).

Workup

  1. customdegassed
  2. customthe reaction mixture was degassed
  3. temperatureto cool
  4. dry with materialThe combined ether portions were dried (MgSO4)
  5. customremoved in vacuo
  6. extractionextracted
  7. filtrationtwice, with diethyl filtered
  8. customthe solvent removed in vacuo
  9. customto give the crude residue

Sources & evidence

ORD record
ord-7483c27d32e04c27bf0d6814d3c81793
Source dataset
uspto-grants-1997_04
Patent number
US05616610

Reaction notes

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