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

HRID 1590793

Reaktionsgleichung

Reaktionsgleichung von HRID 1590793
[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]

Komponenten

10

Edukt 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

Produkt 1

HCID 150163876-[4-(3-carbomethoxy3,3-dimethylpropyloxy)-3-chlorophenyl]-4,5-dihydro-3(2H)-pyridazinoneAusbeute 74,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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 EP0 178,189), 4.52 g (21.6 mmol) of methyl 4-bromo-2,2-dimethylbutyrate (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 water EtOAc, 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-carbomethoxy-3,3-dimethylpropyloxy)-3-chlorophenyl]-4,5-dihydro-3(2H)-pyridazinone as a white crystalline solid, m.p. 109°-110° C. Yield, 75%.

Aufarbeitung

  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) The solvent
  4. customis removed under vacuum
  5. customto give an oily residue
  6. customThe oil is crystallized by the addition of 50 ml of ethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-0f5d6752deef48ab815a54d6365ff6b7
Quelldatensatz
uspto-grants-1993_04
Patentnummer
US05204463

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