Hydrogen Bromide → 6-[4-(3-carbomethoxy3,3-dimethylpropyloxy)-3-chlorophenyl]-4,5-dihydro-3(2H)-pyridazinone

HRID 344647

Reaction equation

HRID 344647 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:10][CH2:11][C:12](=[O:15])[NH:13][N:14]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:17][CH2:18][C:19]([CH3:25])([CH3:24])[C:20]([O:22][CH3:23])=[O:21].CC1(C)CCOC1=O.Br.C(Cl)(=O)C(Cl)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(N(CC)CC)C.CO>[C:20]([C:19]([CH3:25])([CH3:24])[CH2:18][CH2:17][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[CH2:10][CH2:11][C:12](=[O:15])[NH:13][N:14]=2)=[CH:3][C:2]=1[Cl:1])([O:22][CH3:23])=[O:21]

Participants

10

Reactant 6

HCID 260Hydrogen BromideHCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 947462,2-Dimethyl-4-butyrolactoneHCID 14928877Butanoic acid, 4-bromo-2,2-dimethyl-, methyl esterHCID 1355888616-(3-chloro-4-hydroxyphenyl)-4,5-dihydro-3(2H)-pyridazinone

Product 1

HCID 150163876-[4-(3-carbomethoxy3,3-dimethylpropyloxy)-3-chlorophenyl]-4,5-dihydro-3(2H)-pyridazinoneYield 74.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4.05 g (18.0 mmol) of 6-(3-chloro-4-hydroxyphenyl)-4,5-dihydro-3(2H)-pyridazinone (prepared as described in Eur. Pat. application EPO 178,189), 4.52 g (21.6 mmol) of methyl 4-bromo-2,2dimethylbutyrate (prepared by treatment of 2,2-dimethylbutyrolactone with gaseous HBr, conversion to the acid chloride with oxalyl chloride, and treatment with methanol and triethylamine), and 2.99 g (21.6 mmol) of anhydrous K2CO3 in 40 ml of DMF is heated at 100° C. for 4 hrs under N2. The DMF is removed under vacuum, the residue taken up in 300 ml of 50:50 waterEtOAc, the organic phase washed with cold 5% NaOH (50 ml), then water (50 ml), and dried (MgSO4). The solvent is removed under vacuum to give an oily residue The oil is crystallized by the addition of 50 ml of ethyl ether to give 4.75 g of 6-[4-(3-carbomethoxy3,3-dimethylpropyloxy)-3-chlorophenyl]-4,5-dihydro-3(2H)-pyridazinone as a white crystalline solid, m.p. 109°-110° C. Yield, 75%.

Workup

  1. customThe DMF is removed under vacuum
  2. washthe organic phase washed with cold 5% NaOH (50 ml)
  3. dry with materialwater (50 ml), and dried (MgSO4)
  4. customThe solvent is removed under vacuum
  5. customto give an oily residue The oil
  6. customis crystallized by the addition of 50 ml of ethyl ether

Sources & evidence

ORD record
ord-ea825d8626b6484f85ee6d3430e03fe4
Source dataset
uspto-grants-1991_10
Patent number
US05053338

Linked notes

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