Acetic Acid → HCID 67703569, compound

HRID 865690Notes

Reaction equation

HRID 865690 reaction equation
[CH3:1][C:2]1([C:7]2[N:12]=[N:11][C:10]([CH2:13][CH2:14][CH2:15][O:16][C:17]3[C:22]([CH3:23])=[CH:21][C:20]([N:24]4[CH2:28][N:27]=[C:26]([CH:29]([F:31])[F:30])[O:25]4)=[CH:19][C:18]=3[CH3:32])=[CH:9][CH:8]=2)OCC[O:3]1.C(O)(=O)C.Cl.C(=O)(O)[O-].[Na+]>O>[C:2]([C:7]1[N:12]=[N:11][C:10]([CH2:13][CH2:14][CH2:15][O:16][C:17]2[C:18]([CH3:32])=[CH:19][C:20]([N:24]3[CH2:28][N:27]=[C:26]([CH:29]([F:30])[F:31])[O:25]3)=[CH:21][C:22]=2[CH3:23])=[CH:9][CH:8]=1)(=[O:3])[CH3:1]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 67703558HCID 67703558, compound

Product 1

HCID 67703569HCID 67703569, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 0.24 g (0.538 mmol) of 6-(2-methyl-1,3-dioxolan-2-yl)-3-[3-[2,6-dimethyl-4-(5-difluoromethyl-1,2,4-oxadiazol-2-yl)-phenoxy]-propyl]-pyridazine from example 8d, 20 mL of acetic acid, 5 mL of water, and 5 mL of 2M HCl solution was heated to reflux for 24 hr. The reaction mixture was added to a freshly prepared sodium bicarbonate solution, the aqueous layer was extracted with ethyl acetate (4×50 mL), and the combined organic layer was washed with water (50 mL) and brine (100 mL), dried and concentrated in vacuo. The residue was purified by chromatography on MPLC eluting with 30% ethyl acetate/hexane followed by recrystallization from ethyl acetate/hexane to afford 165 mg (76%) of 6-acetyl-3-[3-[2,6-dimethyl-4-(5-difluoromethyl-1,2,4-oxadiazol-2-yl)-phenoxy]-propyl]-pyridazine (Formula I; R1, R2 =3,5-dimethyl, R3 -6-acetyl, R4 =hydrogen, R5 =5-difluoromethyl-1,2,4-oxadiazolyl, Y=1,3-propylene), m.p. 95°-96° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 hr
  3. extractionthe aqueous layer was extracted with ethyl acetate (4×50 mL)
  4. washthe combined organic layer was washed with water (50 mL) and brine (100 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on MPLC
  8. washeluting with 30% ethyl acetate/hexane
  9. customfollowed by recrystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-ff7cc221db0e43dc9ccdb5c116dfdc36
Source dataset
uspto-grants-1996_10
Patent number
US05567717

Reaction notes

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