2,5-Dichloronitrobenzene → Escitalopram

HRID 1669963

Reaktionsgleichung

Reaktionsgleichung von HRID 1669963
[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][CH2:5][C@@:6]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[CH2:23]O)([C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1)[OH:7].C([O-])([O-])=O.[K+].[K+].ClC1C=CC(Cl)=CC=1[N+]([O-])=O.O.O.[C:45]([OH:50])(=[O:49])[C:46]([OH:48])=[O:47]>C(O)(C)C.O.CS(C)=O>[CH3:25][N:2]([CH2:3][CH2:4][CH2:5][C@@:6]1([C:8]2[CH:9]=[CH:10][C:11]([F:14])=[CH:12][CH:13]=2)[O:7][CH2:23][C:16]2[CH:17]=[C:18]([C:19]#[N:20])[CH:21]=[CH:22][C:15]1=2)[CH3:1].[C:46]([OH:48])([C:45]([OH:50])=[O:49])=[O:47].[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][CH2:5][C@:6]1([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[C:15]2[C:16](=[CH:17][C:18]([C:19]#[N:20])=[CH:21][CH:22]=2)[CH2:23][O:7]1

Komponenten

9

Edukt 4

HCID 69772,5-DichloronitrobenzeneHCID 11430Potassium CarbonateHCID 61373Oxalic acid dihydrateHCID 7472057Citadiol, (S)-

Produkt 2

HCID 146570EscitalopramHCID 146571Escitalopram Oxalate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel2×HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
102.5 °C

Versuchsvorschrift

To a solution of 64 Kg of (S)-(−)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile in 300 lit DMSO was added 77.48 Kg of anhydrous K2CO3 and 43.06 Kg of 2,5-dichloronitrobenzene at room temperature and stirred for 16 hours at 100-105° C. To the reaction mixture 3000 ml of water was added at about 30° C. The reaction mixture was extracted with toluene, the toluene layer was washed with water and 5% sodium hydroxide solution and after acid base treatment yielded an oily product. The oil was dissolved in 510 lit of isopropanol at about 30° C. and 20.4 lit water added, stirred for 10 minutes and 20.8 Kg of oxalic acid dihydrate was added and heated to about 70-75° C., stirred, charcolised, cooled and filtered. The filtrate was cooled to 5-10° C. slowly and the resultant solid was filtered, dried at 60° C. and micronised to get the oxalic acid salt of (S)-(+)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile.

Aufarbeitung

  1. extractionThe reaction mixture was extracted with toluene
  2. washthe toluene layer was washed with water and 5% sodium hydroxide solution
  3. customafter acid base treatment yielded an oily product
  4. additionadded
  5. stirringstirred for 10 minutes
  6. temperatureheated to about 70-75° C.
  7. stirringstirred
  8. temperaturecooled
  9. filtrationfiltered
  10. temperatureThe filtrate was cooled to 5-10° C. slowly
  11. filtrationthe resultant solid was filtered
  12. customdried at 60° C.

Quellen und Nachweise

ORD-Eintrag
ord-df9db3506fd244e283d134607df37575
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07989645B2

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