Sodium Carbonate → HCID 70663649, compound

HRID 878234Notes

Reaction equation

HRID 878234 reaction equation
[C:1]([O:5][C:6](=[O:21])[N:7]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1I)[CH2:8][C:9]1([CH3:13])[CH2:12][O:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:47][C:48]1[CH:53]=[CH:52][C:51](B(O)O)=[C:50]([O:57][CH3:58])[CH:49]=1.[NH4+].[Cl-]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[F:47][C:48]1[CH:53]=[CH:52][C:51]([C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[N:7]([CH2:8][C:9]2([CH3:13])[CH2:12][O:11][CH2:10]2)[C:6](=[O:21])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[C:50]([O:57][CH3:58])[CH:49]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acid2×HCID 70663172HCID 70663172, compound

Product 1

HCID 70663649HCID 70663649, compoundYield 298.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4-iodo-pyridin-3-yl)-(3-methyl-oxetan-3-ylmethyl)-carbamic acid tert-butyl ester (0.878 g, 2.17 mmol) in DME (10 mL) under argon 4-fluoro-2-methoxyphenylboronic acid (424 mg, 2.5 mmol, CAS RN 179899-07-1) and 2M aqueous Na2CO3 solution (2.77 mL, 5.54 mmol) were added. After stirring for 30 min. at room temperature, palladium(II) acetate (24.4 mg, 0.109 mmol, CAS RN 3375-31-3) and triphenylphosphine polymer bound (73.0 mg, 0.217 mmol, CAS RN 39319-11-4) were added and the reaction was stirred at reflux (90° C. oil bath temperature) for 22 hours. Another 4-fluoro-2-methoxyphenylboronic acid (111 mg, 0.652 mmol) was added and reaction mixture was refluxed for another 4 hours before another 4-fluoro-2-methoxyphenylboronic acid (111 mg, 0.652 mmol) was added. After stirring at reflux temperature for 18 hours the reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100) to give the title compounds as a light brown oil (0.784 g; 89%). MS (ESI): m/z=403.20 [M+H]+.

Workup

  1. additionwere added
  2. stirringthe reaction was stirred
  3. temperatureat reflux (90° C. oil bath temperature) for 22 hours
  4. customreaction mixture
  5. additionwas added
  6. stirringAfter stirring
  7. temperatureat reflux temperature for 18 hours the reaction mixture
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted twice with EtOAc
  10. washThe organic layers were washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. additiontreated with silica gel
  14. customevaporated
  15. customThe compound was purified by silica gel chromatography on a 20 g column
  16. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-07a80ac690e54f35afdb467dc6cdf599
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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