Dimethylformamide → HCID 66670107, compound

HRID 1014925Notes

Reaction equation

HRID 1014925 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([O:16][Si](C(C)(C)C)(C)C)[CH2:13][CH:12]1[CH:24]=[CH:25][CH2:26][N:27]([C:35](=[O:37])[CH3:36])[C:28]1[C:33](Br)=[CH:32][CH:31]=[CH:30][N:29]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([O-:41])([O-])=O.[K+].[K+].[CH3:44]N(C=O)C>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].C(OCC)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([O:16][C:38](=[O:41])[CH3:44])[CH2:13][CH:12]1[CH2:24][C:25]1[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[N:27]([C:35](=[O:37])[CH3:36])[CH:26]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 66670238HCID 66670238, compound

Product 1

HCID 66670107HCID 66670107, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
85 °C

Procedure

Under a nitrogen atmosphere a solution containing 69 (5.92 g, 10.1 mmol) in anhydrous DMF (50 mL) was charged with (n-Bu)4NCl (2.8 g, 10.1 mmol), K2CO3 (1.4 g, 10.1 mmol), NaHCO2 (0.68 g, 10.1 mmol), and Pd(OAc)2 (0.045 g, 0.20 mmol) at ambient temperature. The heterogeneous mixture was immersed in a pre-heated (85° C.) oil bath. After 3 h, TLC analysis revealed some 69 remained therefore additional catalyst (0.01 g) was added. After an additional 1 h of heating, 69 was completely consumed by TLC analysis [1:1 EtOAc/hexanes, Rf(69) 0.3; Rf(70)=0.8]. The warm reaction mixture was cooled in an ice bath then diluted with diethyl ether and filtered through a pad of celite. The solids were washed with diethyl ether and the filtrate was washed several times with water to remove excess DMF, then washed once with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 5.1 g of crude 70 which was purified by flash silica gel chromatography (20% EtOAc/hexanes) to afford 3.0 g (59%) of 70 as a white solid. 1H NMR (CDCl3, 300 MHz) δ5.18 (m, 1H), 7.60 (m, 1H), 7.18 (m, 1H), 7.05 (dt, J=2.4, 8.7 Hz, 1H), 4.13 (m, 1H), 3.41 (m, 1H), 3.33 (m, 2H), 3.17 (app dd, J=14.1, 38.1 Hz, 1H), 2.61 (s, 3H), 1.83 (m, 3H), 1.69 (m, 1H), 1.49 (s, 94) ppm.

Workup

  1. temperatureAfter an additional 1 h of heating
  2. custom69 was completely consumed by TLC analysis [1:1 EtOAc/hexanes, Rf(69) 0.3; Rf(70)=0.8]
  3. customThe warm reaction mixture
  4. temperaturewas cooled in an ice bath
  5. filtrationfiltered through a pad of celite
  6. washThe solids were washed with diethyl ether
  7. washthe filtrate was washed several times with water
  8. customto remove excess DMF
  9. washwashed once with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto afford 5.1 g of crude 70 which
  14. customwas purified by flash silica gel chromatography (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0b8d1a4d74c8475c99c910ced0ee0133
Source dataset
uspto-grants-2011_07
Patent number
US07985735B2

Reaction notes

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