Water → HCID 118131408, compound

HRID 634426Notes

Reaction equation

HRID 634426 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH2:3][O:2]1.O=P(Cl)(Cl)Cl.C(#N)C.O.[CH2:21]([Cl:23])Cl>CN(C=O)C.C(O)=O>[Cl:23][C:21]1[C:9]2[C:10](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:1][O:2][C:3]=1[CH:4]=[O:11]

Participants

8

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 6344Dichloromethane2×HCID 24813Phosphorus oxychlorideHCID 123396483,4-dihydro-1H-2-benzopyran-4-one

Product 1

HCID 118131408HCID 118131408, compoundYield 60.6%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To commercially available isochroman-4-one (900 mg, 6.07 mmol) in DCM (18 ml), DMF (0.706 ml) and POCl3 (1.699 ml, 18.23 mmol) were added in sequence under Nitrogen at r.t. The mixture was refluxed for 6 h and kept at r.t overnight. The reaction mixture was diluted with DCM (15 ml), washed with water and sat NaCl, then anhydrified over Na2SO4 and evaporated in vacuo. The resulting crude was purified via reverse phase chromatography with a Biotage C18 SNAP 30 g column (Phase A, water 95%, ACN 5%, formic acid 0.1%); Phase B ACN 95%, water 5%, formic acid 0.1%) to give 4-chloro-1H-isochromene-3-carbaldehyde (Intermediate G20.1, 716 mg, 60.6% yield)

Workup

  1. temperatureThe mixture was refluxed for 6 h
  2. washwashed with water
  3. customevaporated in vacuo
  4. customThe resulting crude was purified via reverse phase chromatography with a Biotage C18 SNAP 30 g column (Phase A, water 95%, ACN 5%, formic acid 0.1%)

Sources & evidence

ORD record
ord-a40045dd22b54889abc0668bac39b539
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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