Sodium Bicarbonate → 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]2-hydroxy-5-methoxyphenyl]ethanone

HRID 567540Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 567540
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.Cl[CH2:18][CH2:19][CH2:20][O:21][C:22]1[C:27]([O:28][CH3:29])=[CH:26][C:25]([C:30](=[O:32])[CH3:31])=[C:24]([OH:33])[CH:23]=1.C([O-])(O)=O.[Na+]>>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:18][CH2:19][CH2:20][O:21][C:22]4[C:27]([O:28][CH3:29])=[CH:26][C:25]([C:30](=[O:32])[CH3:31])=[C:24]([OH:33])[CH:23]=4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Komponenten

4

Edukt 3

HCID 516892Sodium BicarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 184672431-[4-(3-Chloropropoxy)-2-hydroxy-5-methoxyphenyl]ethanone

Produkt 1

HCID 224570921-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]2-hydroxy-5-methoxyphenyl]ethanoneAusbeute 13,1 %

Versuchsvorschrift

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.2 g, 19 mmol), 1-[4-(3-chloropropoxy)-2-hydroxy-5-methoxyphenyl]ethanone (5.0 g, 19 mmol), NaHCO3 (1.8 g, 20 mmol) and acetronitrile (120 mL) was stirred and refluxed for 16 hours. The reaction was filtered and the filtrate was concentrated to a dark oil. The oil was taken up in anhydrous ether and ethereal HCl was added to precipitate 8.7 g of an off-white hydrochloride salt. A 2.0 g sample of the salt was converted to its free base and chromatographed by preparative HPLC (silica gel with 5% MeOH/CH2Cl2 as eluent). Concentration of the desired fractions gave 1.1 g of a white solid, which was recrystallized from EtOH to yield 0.85 g of the product, m.p. 122°-124° C.

Aufarbeitung

  1. temperaturerefluxed for 16 hours
  2. filtrationThe reaction was filtered
  3. concentrationthe filtrate was concentrated to a dark oil
  4. additionethereal HCl was added
  5. customto precipitate 8.7 g of an off-white hydrochloride salt
  6. customchromatographed by preparative HPLC (silica gel with 5% MeOH/CH2Cl2 as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-1b2f70de8f20464e96372cbe57461035
Quelldatensatz
uspto-grants-2001_01
Patentnummer
USRE037029E1

Notizen zur Reaktion

Wird geladen…