Potassium Carbonate → HCID 66809318, compound

HRID 1014922Notes

Reaction equation

HRID 1014922 reaction equation
[C:1]([N:4]([C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1Br)[CH2:5][CH:6]=[CH:7][CH:8]1[CH:12]([CH3:13])[CH2:11][CH2:10][N:9]1[C:14]([OH:16])=[O:15])(=[O:3])[CH3:2].C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:12]([O:16][C:14]([N:9]1[CH2:10][CH2:11][CH:12]([CH3:13])[CH:8]1[CH2:7][C:6]1[C:18]2[C:17](=[CH:22][C:21]([F:23])=[CH:20][CH:19]=2)[N:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)=[O:15])([CH3:13])([CH3:8])[CH3:11]

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 66670067HCID 66670067, compound

Product 1

HCID 66809318HCID 66809318, compoundYield 106.8%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution containing 64 (5 g, 0.011 mol), n-Bu4NCl (3.3 g, 0.012 mol), K2CO3 (1.65 g, 0.012 mol), and NaHCO2 (0.81 g, 0.012 mol) in DMF (20 mL) was degassed under high vacuum. Palladium acetate (0.49 g, 0.002 mol) was added and the heterogeneous reaction mixture was immersed in a preheated (80-85° C.) oil bath. After 3 h, TLC analysis revealed complete consumption of 64 [1:1 hexane/EtOAc, Rf(64)=0.4, Rf(65)=0.5]. The reaction mixture was cooled in an ice bath and diethyl ether (100 mL) was added. The mixture was filtered through Celite® and the solids were washed with diethyl ether. The filtrate was washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by normal phase HPLC (10-100% EtOAc/hexane over 50 min) to afford 2.2 g (54%) of 65 as brown, viscous oil. 1H NMR (CDCl3, 300 MHz) δ8.22-8.1 (m, 1H), 7.7-7.5 (m, 1H), 7.15-6.97 (m, 2H), 3.8-2.65 (m, 4H), 2.6 (s, 3H), 2.12-1.85 (m, 1H), 1.62 (s, 1H), 1.42 (s, 9H, major rotamer), 1.4 (s, minor rotamer), 0.9 (d, J=6 Hz, 3H) ppm. Mass spectrum, m/z=274.5 (M-BOC)+.

Workup

  1. customwas degassed under high vacuum
  2. customwas immersed in a preheated (80-85° C.) oil bath
  3. customconsumption of 64 [1:1 hexane/EtOAc, Rf(64)=0.4, Rf(65)=0.5]
  4. temperatureThe reaction mixture was cooled in an ice bath
  5. additiondiethyl ether (100 mL) was added
  6. filtrationThe mixture was filtered through Celite®
  7. washthe solids were washed with diethyl ether
  8. washThe filtrate was washed with water, brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was purified by normal phase HPLC (10-100% EtOAc/hexane over 50 min)

Sources & evidence

ORD record
ord-3a05a8aaf53f440896b71412a2c680e7
Source dataset
uspto-grants-2011_07
Patent number
US07985735B2

Reaction notes

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