Dimethylformamide → HCID 86640983, compound

HRID 906472Notes

Reaction equation

HRID 906472 reaction equation
[C:1]([O:7][CH2:8][C:9]([CH3:24])([CH3:23])[CH2:10][N:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Br:21])[CH:17]=2)[C:12]1=[O:22])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].O=P(Cl)(Cl)Cl.CN([CH:33]=[O:34])C>>[C:1]([O:7][CH2:8][C:9]([CH3:24])([CH3:23])[CH2:10][N:11]1[CH:20]=[C:19]([CH:33]=[O:34])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Br:21])[CH:17]=2)[C:12]1=[O:22])(=[O:6])[C:2]([CH3:4])([CH3:5])[CH3:3]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 67390345HCID 67390345, compound

Product 1

HCID 86640983HCID 86640983, compound

Procedure

A stirred solution of 3-(6-bromo-1-oxoisoquinolin-2(1H)-yl)-2,2-dimethylpropyl pivalate (51.3 g) in DMF (150 mL) at 75° C. (flask fitted with a CaCl2 drying tube) was treated dropwise over ˜20 min with a freshly prepared solution of Vilsmeyer Haak reagent [freshly prepared by dropwise addition of POCl3 (182 mL) over ˜40 min to DMF (302 mL) at 0° C. and then stirred for 1 h at room temperature]. Heating was continued for 8 h, and then the reaction mixture was cooled to room temperature and stirred overnight. The mixture was poured onto ice water (6 L) [CAUTION: exotherm] and extracted with tert-butyl methyl ether (2×2.5 L). The combined organics were washed with 20% w/v aqueous brine (2.5 L), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified (SiO2 chromatography, eluting with 10% to 20% ethyl acetate/isohexane) to give the subtitle product (41.5 g).

Workup

  1. additionwas treated dropwise over ˜20 min with a freshly prepared solution of Vilsmeyer Haak reagent [
  2. temperatureHeating
  3. waitwas continued for 8 h
  4. temperaturethe reaction mixture was cooled to room temperature
  5. stirringstirred overnight
  6. additionThe mixture was poured onto ice water (6 L) [CAUTION: exotherm]
  7. extractionextracted with tert-butyl methyl ether (2×2.5 L)
  8. washThe combined organics were washed with 20% w/v aqueous brine (2.5 L)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified
  13. wash(SiO2 chromatography, eluting with 10% to 20% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-65f702869dc04a3a9d7528da5f0866ff
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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