1-Bromo-3,5-difluorobenzene → HCID 86758170, compound

HRID 2186404Notes

Reaction equation

HRID 2186404 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=1.[CH3:10][O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[CH:17][CH:16]=[C:15]2[CH2:22][CH2:23][CH2:24][C@@H:25]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]#[CH:33])[CH2:27][C@@H:26]1[CH2:34][C:35]([O:37][CH3:38])=[O:36]>C(N(CC)CC)C.C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:10][O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[CH:17][CH:16]=[C:15]2[CH2:22][CH2:23][CH2:24][C@@H:25]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]#[C:33][C:2]2[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=2)[CH2:27][C@@H:26]1[CH2:34][C:35]([O:37][CH3:38])=[O:36]

Participants

7

Reactant 2

HCID 1363131-Bromo-3,5-difluorobenzeneHCID 86758171HCID 86758171, compound

Product 1

HCID 86758170HCID 86758170, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

0.35 cm3 of 1-bromo-3,5-difluorobenzene and then 0.112 g of tetrakis(triphenylphosphine)palladium and 0.037 g of cuprous iodide were added at a temperature in the region of 20° C., under an inert atmosphere, to a stirred mixture of 0.77 g of methyl (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-acetate in 7.7 cm3 of triethylamine. The suspension obtained was heated at a temperature in the region of 80° C. for 3 hours and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in 50 cm3 of ethyl acetate in 20 cm3 of water. After stirring the mixture for 15 minutes, the remaining insoluble material was filtered through clarcel and then the filtrate was separated by settling: the organic phase was separated off, then washed with 3 times 3 cm3 of water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The oily residue obtained was purified by. chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 40-63μ; diameter 3 cm; 45 g), elution was carried out with a dichloromethane/methanol (97/3 by volume) mixture. The fractions comprising the expected product were collected. These fractions were concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.345 g of methyl (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(3,5-difluorophenyl)prop-2-ynyl]piperidine-3-acetate was obtained in the form of an oil with a pale yellow color. Mass spectrum (El): m/z=506 M+.

Workup

  1. customThe suspension obtained
  2. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. filtrationthe remaining insoluble material was filtered through clarcel
  5. customthe filtrate was separated
  6. customthe organic phase was separated off
  7. washwashed with 3 times 3 cm3 of water
  8. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  11. customThe oily residue obtained
  12. customwas purified by
  13. washchromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 40-63μ; diameter 3 cm; 45 g), elution
  14. customwere collected
  15. concentrationThese fractions were concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-8707531970194855af53c4633568eb06
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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