Chlorosuccinimide → Methyl 3-cyano-4-isopropoxybenzoate

HRID 222911Notes

Reaction equation

HRID 222911 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[OH:13])[C:6]([O:8][CH3:9])=[O:7])#[N:2].ClN1C(=O)[CH2:18][CH2:17][C:16]1=O>C(#N)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][CH:17]([CH3:18])[CH3:16])[C:6]([O:8][CH3:9])=[O:7])#[N:2]

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 11769089Methyl 3-cyano-4-hydroxybenzoate

Product 1

HCID 21956805Methyl 3-cyano-4-isopropoxybenzoateYield 80.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A portion of residue 3 (4.19 g, ˜7.45 mmol) was dissolved in acetonitrile (50 mL) and treated with N-chlorosuccinimide (1.19 g, 8.94 mmol) at room temperature. The temperature was raised to 65° C. and the mixture stirred overnight. When LC/MS showed complete conversion of starting material, the mixture was cooled to room temperature and partitioned between water (150 mL) and ethyl acetate (150 mL). The organic layer was separated and the organic phase washed twice with 2 N Na2CO3 and brine, dried over Na2SO4 and concentrated under vacuum to give an off white solid. The product was purified by preparative reverse phase HPLC to give pure desired product 4 (1.31 g, 29% from s.m.) as a white foamy solid upon solvent evaporation and high vacuum drying. LRMS (M+H+) m/z 598.0.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. custompartitioned between water (150 mL) and ethyl acetate (150 mL)
  3. customThe organic layer was separated
  4. washthe organic phase washed twice with 2 N Na2CO3 and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customto give an off white solid
  8. customThe product was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-2d9225190dd642a6a946f0b9b83dc13c
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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