Oxygen → 1-[3-(Pentafluorosulfanyl)-5-pyrrolidin-1-ylphenyl]ethanone

HRID 1258536Notes

Reaction equation

HRID 1258536 reaction equation
Br[C:2]1[CH:7]=[C:6]([S:8]([F:13])([F:12])([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:14]([O:18]C)(OC)[CH3:15])[CH:3]=1.O=O.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.CC(C)([O-])C.[Na+]>COCCOC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(=O)OCC>[F:13][S:8]([F:10])([F:11])([F:12])([F:9])[C:6]1[CH:5]=[C:4]([C:14](=[O:18])[CH3:15])[CH:3]=[C:2]([N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:7]=1

Participants

10

Reactant 4

HCID 977OxygenHCID 31268PyrrolidineHCID 23676156Sodium t-butoxideHCID 581374181-Bromo-3-(1,1-dimethoxyethyl)-5-(pentafluorosulfanyl)benzene

Product 1

HCID 581374371-[3-(Pentafluorosulfanyl)-5-pyrrolidin-1-ylphenyl]ethanone

Reagents, catalysts & solvents 5

HCID 962WaterCatalystHCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 80711,2-DimethoxyethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

1-Bromo-3-(1,1-dimethoxyethyl)-5-(pentafluorosulfanyl)benzene (200 mg) was initially charged at RT in DME (30 ml) under argon. Two drops of water were added to the DME. A strong argon stream was used to displace the oxygen from the solution for 45 min. Then pyrrolidine (45 μl) was added dropwise through a septum, followed by (+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (5 mg), sodium tert-butoxide (73 mg) and palladium(II) acetate (1.2 mg). The reaction mixture was heated to 85° C. for 3 h. Then EA was added to the reaction mixture and, after removing the EA phase, the aqueous phase was extracted three times with EA. The combined EA phases were dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in ACN/water and adjusted to pH 2 with 1N hydrochloric acid. After standing for 30 min, the mixture was concentrated and the residue was purified by means of preparative HPLC. The product-containing fractions were combined, freed of the acetonitrile, admixed with saturated sodium hydrogencarbonate solution and extracted three times with ethyl acetate. The combined extracts were dried over magnesium sulfate, filtered and concentrated. 55 mg of the desired compound were obtained.

Workup

  1. customfor 45 min
  2. customafter removing the EA phase
  3. extractionthe aqueous phase was extracted three times with EA
  4. dry with materialThe combined EA phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in ACN/water
  8. concentrationthe mixture was concentrated
  9. customthe residue was purified by means of preparative HPLC
  10. extractionextracted three times with ethyl acetate
  11. dry with materialThe combined extracts were dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-9b7c41b31b20490cade1bc61205da32d
Source dataset
uspto-grants-2013_06
Patent number
US08466169B2

Reaction notes

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