Ethyl chloroformate → HCID 69019446, compound

HRID 1865133Notes

Reaction equation

HRID 1865133 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([C:21]#[N:22])=[N:17][N:18]([CH3:20])[CH:19]=2)=[CH:11][CH:10]=1)#[N:2].C([Li])CCC.Cl[C:29]([O:31][CH2:32][CH3:33])=[O:30]>C1COCC1>[CH2:32]([O:31][C:29]([C:19]1[N:18]([CH3:20])[N:17]=[C:16]([C:21]#[N:22])[C:15]=1[C:12]1[CH:11]=[CH:10][C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:1]#[N:2])=[CH:14][CH:13]=1)=[O:30])[CH3:33]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 69020814HCID 69020814, compoundHCID 178418339Butyllithium

Product 1

HCID 69019446HCID 69019446, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

Prepare a solution of 4-(2′-cyano-biphenyl-4-yl)-1-methyl-1H-pyrazole-3-carbonitrile (101 mg, 0.355 mmol, prepared in preparation 46) in 3 mL of anhydrous THF and cool to −70° C. Add n-butyl lithium (1.6M in hexanes, 0.2 mL, 0.32 mmol) dropwise, keeping the internal temperature less than −65° C. Stir the orange solution for 30 minutes at −70° C. Next, add ethyl chloroformate (0.1 mL, 1.02 mmol) and allow the reaction to warm to room temperature over one hour. Quench with 2 mL of saturated NH4Cl and dilute with 50 mL of EtOAc. Wash the organic layer with water (1×10 mL) and brine (1×10 mL) and dry over anhydrous Na2SO4. Filter, evaporate and chromatograph over silica gel (100/0-7/3 toluene/EtOAc) to give the title compound, 37 mg (29%) along with 38 mg of recovered starting material.

Workup

  1. customthe internal temperature less than −65° C
  2. customthe reaction
  3. temperatureto warm to room temperature over one hour
  4. customQuench with 2 mL of saturated NH4Cl
  5. additiondilute with 50 mL of EtOAc
  6. washWash the organic layer with water (1×10 mL) and brine (1×10 mL)
  7. dry with materialdry over anhydrous Na2SO4
  8. filtrationFilter
  9. customevaporate

Sources & evidence

ORD record
ord-708e7bfc6ff34681924143d540ef1695
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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