Water → HCID 89494760, compound

HRID 531416Notes

Reaction equation

HRID 531416 reaction equation
O=P(Cl)(Cl)Cl.O.[C:7](=[O:10])(O)[O-].[Na+].[CH:12]([N:15]([CH2:23][C:24]#[CH:25])[C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1)([CH3:14])[CH3:13]>CN(C=O)C>[OH:22][C:18]1[CH:17]=[C:16]([N:15]([CH:12]([CH3:14])[CH3:13])[CH2:23][C:24]#[CH:25])[CH:21]=[CH:20][C:19]=1[CH:7]=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 89494805HCID 89494805, compound

Product 1

HCID 89494760HCID 89494760, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

After DMF (13.30 mL, 172.6 mmol) was cooled to 0° C. and POCl3 (2.68 mL, 28.79 mmol) was added dropwise thereto, the mixture was stirred for 20 minutes, warmed to room temperature, and then stirred for 1 hour. To this reactant, a solution in which the 3-(isopropyl(prop-2-ynyl)amino)phenol compound of Chemical Formula 3 (2.18 g, 11.51 mmol) was dissolved in DMF (10 mL) was added, and then the mixture was stirred for 12 hours. Distilled water (30 mL) was added to the post-reaction mixture, and the result was neutralized to between pH 7 and 8 by adding sodium bicarbonate solid. After this mixture was partitioned to acetic acid (100 mL) and distilled water (30 mL), the organic layer was separated, washed with saturated salted water (10 mL), dried with anhydrous sodium sulfate, filtered and vacuum distilled, and the residue obtained was column chromatographed on silica gel (hexane/ethyl acetate (7:1)) to give 2-hydroxy-4-(isopropyl(prop-2-ynyl)amino)benzaldehyde (2.05 g, 82%). 1H NMR (500 MHz, CDCl3) d 11.52 (s, 1H), 9.55 (s, 1H), 7.33 (d, 1H, J=8.7 Hz), 6.46 (dd, 1H, J=2.3, 8.7 Hz), 6.29 (d, 1H, J=2.3 Hz), 4.19-4.22 (m, 1H), 3.98 (d, 2H, J=2.7 Hz), 2.23 (t, 1H, J=2.7 Hz), 1.29 (d, 6H, J=6.9 Hz); 13C NMR (125 MHz, CDCl3) d 192.7, 164.2, 154.7, 135.3, 112.4, 105.4, 98.5, 80.4, 72.0, 49.1, 33.3, 20.2 (2).

Workup

  1. stirringstirred for 1 hour
  2. additionwas added
  3. stirringthe mixture was stirred for 12 hours
  4. customAfter this mixture was partitioned to acetic acid (100 mL)
  5. distillationdistilled water (30 mL)
  6. customthe organic layer was separated
  7. washwashed with saturated salted water (10 mL)
  8. dry with materialdried with anhydrous sodium sulfate
  9. filtrationfiltered
  10. distillationvacuum distilled
  11. customthe residue obtained
  12. customchromatographed on silica gel (hexane/ethyl acetate (7:1))

Sources & evidence

ORD record
ord-c552521f5fda4858855d2a45281f00c9
Source dataset
uspto-grants-2016_05
Patent number
US09354234B2

Reaction notes

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