Dimethylformamide → 3-(3,5-Dichloro-4-formylphenyl)-propionic acid tert-butyl ester

HRID 1513290Notes

Reaction equation

HRID 1513290 reaction equation
[C:1]([O:5][C:6](=[O:17])[CH2:7][CH2:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[C:11]([Cl:16])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])(CC)C.CN([CH:26]=[O:27])C>C1COCC1>[C:1]([O:5][C:6](=[O:17])[CH2:7][CH2:8][C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([CH:26]=[O:27])=[C:11]([Cl:16])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 669653423-(3,5-Dichlorophenyl)-propionic acid tert-butyl esterHCID 178418400CID 53628100

Product 1

HCID 866328253-(3,5-Dichloro-4-formylphenyl)-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(3,5-Dichloro-phenyl)-propionic acid tert butyl ester (1 g, 3.6 mmol) in THF (50 mL) at −78 C was added dropwise s-butyl lithium (1.4 M cyclohexanes; 5.7 mL, 2.2 eq). The resulting red colored homogeneous solution was stirred under nitrogen at −78C for one hour, at which time DMF (560 mL, 2 eq) was added. After 30 minutes, quenched reaction with saturated ammonium chloride solution at −78 C. Removed ice bath and allowed reaction to reach room temperature. Evaporation of volatiles in vacuo, partitioned between water and ethyl acetate. Combined ethyl acetate fractions were dried over magnesium sulfate and appropriately loaded onto a silica gel column. Isolated 600 mg of titled compound after chromatography (isocratic 20% ethyl acetate/n-heptanes). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.35-1.44 (m, 10 H) 2.55 (t, J=7.45 Hz, 2 H) 2.90 (t, J=7.45 Hz, 2 H) 7.23 (s, 2 H) 10.45 (s, 1 H).

Workup

  1. waitAfter 30 minutes
  2. customquenched
  3. customreaction with saturated ammonium chloride solution at −78 C
  4. customRemoved ice bath and allowed
  5. customreaction
  6. customto reach room temperature
  7. customEvaporation of volatiles in vacuo
  8. custompartitioned between water and ethyl acetate
  9. dry with materialCombined ethyl acetate fractions were dried over magnesium sulfate

Sources & evidence

ORD record
ord-7e18381944384dbaa4048f8da8cfaf98
Source dataset
uspto-grants-2012_07
Patent number
US08217065B2

Reaction notes

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