Diethyl cyanophosphonate → 2-(Isochroman-1-yl)-1-[4-(4-ethoxyphenyl)piperazin-1-yl]-2-methylpropan-1-one

HRID 1417821

Reaktionsgleichung

Reaktionsgleichung von HRID 1417821
[CH:1]1([CH2:11][C:12](O)=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][O:2]1.Cl.Cl.[CH2:17]([O:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1)[CH3:18].[C:32](P(=O)(OCC)OCC)#N.[C:42](=[O:45])(O)[O-].[Na+]>ClCCl.CN(C=O)C.C(N(CC)CC)C>[CH:1]1([C:11]([CH3:12])([CH3:32])[C:42]([N:29]2[CH2:28][CH2:27][N:26]([C:23]3[CH:22]=[CH:21][C:20]([O:19][CH2:17][CH3:18])=[CH:25][CH:24]=3)[CH2:31][CH2:30]2)=[O:45])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][O:2]1

Komponenten

8

Edukt 4

HCID 76257Diethyl cyanophosphonateHCID 516892Sodium BicarbonateHCID 133088642-(3,4-dihydro-1H-2-benzopyran-1-yl)acetic acidHCID 232887411-(4-Ethoxyphenyl)piperazine dihydrochloride

Produkt 1

HCID 232888992-(Isochroman-1-yl)-1-[4-(4-ethoxyphenyl)piperazin-1-yl]-2-methylpropan-1-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Triethylamine (0.48 ml) is added to a mixture of (-)-(isochroman-1-yl)acetic acid (LXI, EXAMPLE 45 Step 3, 0.2016 g, 1.05 mmol), DMF (1.1 ml), dichloromethane (1.1 ml), 1-(4-ethoxyphenyl)piperazine dihydrochloride (XXIV, 0.2997 g, 1.07 mmol) and diethyl cyanophosphonate (0.21 ml). After 2 hr, saturated sodium bicarbonate is added and the mixture is stirred for 2 hr and then extracted several times with dichloromethane. The combined organic phases are backwashed with saline, dried over magnesium sulfate, concentrated, and the residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give a residue which upon crystallization from ethyl acetate/hexane gives 2-(isochroman-1-yl)-1-[4-(4-ethoxyphenyl)piperazin-1-yl]-2-methylpropan-1-one (LXXXII), MS (m/z) 380; IR (mineral oil) 1620, 1248, 1515, 1107, 1444 and 815 cm-1.

Aufarbeitung

  1. extractionextracted several times with dichloromethane
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. customthe residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98)
  5. concentrationconcentrated
  6. customto give a residue which
  7. customupon crystallization from ethyl acetate/hexane

Quellen und Nachweise

ORD-Eintrag
ord-2e2def5ebde747dab13b6498daee1bff
Quelldatensatz
uspto-grants-1999_03
Patentnummer
US05877317

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