Hydrochloric Acid → 2-cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxymethyl-2H-pyridazin-3-one

HRID 2249409Notes

Reaction equation

HRID 2249409 reaction equation
[C:1]([C:4]1[C:5](=[O:23])[N:6]([CH2:19][CH:20]2[CH2:22][CH2:21]2)[N:7]=[C:8]([C:10]2[CH:11]=[CH:12][C:13]3[O:17][CH2:16][CH2:15][C:14]=3[CH:18]=2)[CH:9]=1)(O)=[O:2].C(N(CC)CC)C.C(=O)([O-])OCCCl.[BH4-].[Na+].Cl>C1COCC1.O>[CH:20]1([CH2:19][N:6]2[C:5](=[O:23])[C:4]([CH2:1][OH:2])=[CH:9][C:8]([C:10]3[CH:11]=[CH:12][C:13]4[O:17][CH2:16][CH2:15][C:14]=4[CH:18]=3)=[N:7]2)[CH2:22][CH2:21]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 22631361Chloroethyl carbonateHCID 230941314-carboxy-2-cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-2H-pyridazin-3-one

Product 1

HCID 230941232-cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxymethyl-2H-pyridazin-3-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-carboxy-2-cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-2H-pyridazin-3-one (1.8 g, 5.76 mmol) in THF (25 mL), triethylamine (641 mg, 6.34 mmol) was added, and a solution of chloroethyl carbonate (688 mg, 6.34 mmol) in THF (1 mL) was added dropwise to the resultant mixture under cooling with ice, followed by stirring for 30 minutes. The formed triethylamine hydrochloride was removed through filtration, and a solution of sodium borohydride (327 mg, 8.64 mmol) in water (2 mL) was added to the filtrate under cooling with ice, followed by stirring for 15 minutes at room temperature. Aqueous hydrochloric acid (2 mol/L) was added to the reaction mixture, and the resultant mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate anhydrate. The solvent was removed under reduced pressure, and the residue was subjected to a separation/purification step through silica gel column chromatography [silica gel 60 g, chloroform/methanol (100/1)], to thereby yield 566 mg of the title compound as pale yellow powder (32.9%).

Workup

  1. temperatureunder cooling with ice
  2. customThe formed triethylamine hydrochloride was removed through filtration
  3. temperatureunder cooling with ice
  4. stirringby stirring for 15 minutes at room temperature
  5. extractionthe resultant mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over sodium sulfate anhydrate
  8. customThe solvent was removed under reduced pressure
  9. customthe residue was subjected to a separation/purification step through silica gel column chromatography [silica gel 60 g, chloroform/methanol (100/1)]

Sources & evidence

ORD record
ord-a8514653ee824cc68f8b45ac9a60702a
Source dataset
uspto-grants-2008_01
Patent number
US07314877B2

Reaction notes

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