Triethylamine → (R)-8-Fluoro-5-methoxycarbonyl-3-(N,N-di-n-propylamino)chroman

HRID 2257359Notes

Reaction equation

HRID 2257359 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5](OS(C(F)(F)F)(=O)=O)=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([N:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:7]2.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN([CH:66]=[O:67])C.[CH3:68][OH:69]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:68]([O:67][CH3:66])=[O:69])=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([N:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:7]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 21901440N,N-dimethylformamide methanolHCID 22853674HCID 22853674, compound

Product 1

HCID 54215077(R)-8-Fluoro-5-methoxycarbonyl-3-(N,N-di-n-propylamino)chromanYield 87%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

(R)-8-Fluoro-3-(N,N-di-n-propylamino)-5-trifloromethanesulfonyloxychroman (0.95 g, 2.4 mmol), triethylamine (0.53 g, 5.2 mmol), 1,3-bis(diphenylphosphino)propane (100 mg, catalytic amount), palladium(II)acetate (50 mg, catalytic amount) and DMF/MeOH (18 mL, 6:2) were mixed in a 50 mL three necked round bottom flask. The flask was evacuated followed by the inlet of CO (repeated three times). The reaction mixture was stirred at 70° C. for 7 hours. The solvent was removed in vacuo and the residue was dissolved in diethyl ether/2M NH3. The layers were separated and the water phase was extracted once with ether. The combined ether layers were dried (MgSO4) and the solvent was removed in vacuo to give a brown oily residue which was purified by flash chromatography (SiO2, CH2Cl2 /EtOAC, 20:1) to give 650 mg of the title compound as a clear oil (87% yield). [α]D21 -92° (c 10 mg/mL, MeOH). Mass spectrum (70 eV) m/Z (relative intensity) 309(20, M+), 281(18), 280(100), 56(10), 43(22), 42(12), 41(16).

Workup

  1. customThe flask was evacuated
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in diethyl ether/2M NH3
  4. customThe layers were separated
  5. extractionthe water phase was extracted once with ether
  6. dry with materialThe combined ether layers were dried (MgSO4)
  7. customthe solvent was removed in vacuo
  8. customto give a brown oily residue which
  9. customwas purified by flash chromatography (SiO2, CH2Cl2 /EtOAC, 20:1)

Sources & evidence

ORD record
ord-43851e38caae4eeab05ff85661ef9cf6
Source dataset
uspto-grants-1997_08
Patent number
US05656658

Reaction notes

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