Cesium carbonate → HCID 66756714, compound

HRID 1642631Notes

Reaction equation

HRID 1642631 reaction equation
C(O[C:4](=O)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:7]=1)C.[CH2:24]([O:31][C:32]1[CH:39]=[CH:38][CH:37]=C(F)[C:33]=1[C:34]#[N:35])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[CH2:24]([O:31][C:32]1[CH:39]=[CH:38][CH:37]=[C:4]([CH2:5][C:6]2[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:7]=2)[C:33]=1[C:34]#[N:35])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 30234826-Benzyloxy-2-fluorobenzonitrileHCID 66757012HCID 66757012, compound

Product 1

HCID 66756714HCID 66756714, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(3-Benzyloxy-4-nitrophenyl)-acetic acid ethyl ester (Step C) (1.90 g, 6.03 mmol) and 2-benzyloxy-6-fluorobenzonitrile (Step D) (2.74 g, 12.1 mmol) are dissolved in DMF (18 mL) and added dropwise to a suspension of Cs2CO3 (5.89 g, 18.1 mmol) in DMF (18 mL). The mixture is heated to 80° C. for 1.5 h, then stirred at 60° C. for 16 h. The mixture is diluted with EtOAc (350 mL) and extracted with 1N HCl (2×75 mL), followed by brine (75 mL). The organic phase is dried over Na2SO4 and concentrated. The residue is taken up in THF (18 mL), MeOH (18 mL) and 1N NaOH (36 mL). Decarboxylation is complete after 2 h, the reaction mixture is poured into ice water (100 mL) and acidified to pH ˜2 with 6N HCl. The mixture is extracted with EtOAc (2×200 mL) and the organic phase is washed with brine (75 mL), dried over Na2SO4 and concentrated to afford a brown oil. Purification by flash column (10-75% EtOAc/hexanes) affords 2-benzyloxy-6-(3-benzyloxy-4-nitrobenzyl)-benzonitrile as an off-white solid: MS (M+H)+=451.

Workup

  1. extractionextracted with 1N HCl (2×75 mL)
  2. dry with materialThe organic phase is dried over Na2SO4
  3. concentrationconcentrated
  4. waitDecarboxylation is complete after 2 h
  5. additionthe reaction mixture is poured into ice water (100 mL)
  6. extractionThe mixture is extracted with EtOAc (2×200 mL)
  7. washthe organic phase is washed with brine (75 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customto afford a brown oil
  11. customPurification by flash column (10-75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-00bf8f5ff598478faba2a154eb9d0b80
Source dataset
uspto-grants-2012_02
Patent number
US08119666B2

Reaction notes

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