Toluene → HCID 23504870, Verbindung

HRID 351756

Reaktionsgleichung

Reaktionsgleichung von HRID 351756
C[N:2](C)[CH:3]=[O:4].[N+:6]([C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][CH2:14][CH:15]2C(O)=O)=[CH:11][CH:10]=1)([O-:8])=[O:7].S(Cl)(Cl)=O.C1(C)C=CC=CC=1>ClCCl>[N+:6]([C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][CH2:14][CH:15]2[C:3]([NH2:2])=[O:4])=[CH:11][CH:10]=1)([O-:8])=[O:7]

Komponenten

6

Edukt 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 123184886-Nitro-2,3-dihydro-1H-indene-1-carboxylic acid2×

Produkt 1

HCID 23504870HCID 23504870, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Dimethylformamide (DMF, 1 ml) was added to a solution of 6-nitro-1-indancarboxylic acid, 1a (13 g) and thionylchloride (18 ml) in dichloromethane (125 ml). The mixture was heated to reflux for 4 hours. Toluene was added and volatile material was evaporated in vacuo. The thus obtained carboxylic acid chloride was dissolved in dichloromethane (100 ml) and added dropwise to a solution of 4-(4-fluorophenyl)piperidine (19.5 g) and triethylamine (7 ml) in dichloromethane (100 ml) at 0-5° C. The mixture was stirred at room temperature for another 1.5 hours. Water was added, the organic phase separated, washed with brine, dried (anh. MgSO4), filtered, and dichloromethane evaporated in vacuo leaving the crude 6-nitroindan-1-carboxamide derivative as an oil (35 g). Purification by column chromatography on silica gel (eluted with a 1:1 mixture of ethyl acetate and heptane) yielded 12 g of the pure carboxamide as an oil. All of this oil was dissolved in refluxing 90% ethanol (350 ml). Fe-powder (10 g) and concentrated aqueous HCl (1 ml) were added successively in small portions during 10 minutes. The resulting mixture was refluxed for another 2.5 hours. Inorganic salts were filtered off while still hot and ethanol evaporated in vacua, Diluted aqueous NH4OH was added until pH>9. Extraction with ethyl acetate (2×200 ml) and working-up as above of the organic phase afforded 8 g of the 6-aminoindan-1-carboxamide derivative. Mp: 144-145° C. To a suspension of LiAlH4 (2.7 g) in dry tetrahydrofuran (THF, 125 ml) was added dropwise a solution of all of the carboxamide in THF (125 ml). The mixture was gently refluxed for 2 hours. After cooling to 10° C. water (10 ml ) and a 15% aqueous NaOH solution were cautiously added to destroy excess LiAlH4. Inorganic salts were filtered off and washed extensively with THF. The combined THF solutions were evaporated leaving 6.5 g of the title compound 2a as an oil. The hydrochloride salt crystallized from 2-propanol. Mp: 198-201° C. 1H NMR (DMSO-d 6): δ 1.85-2.40 (m, 6H); 2.60-2.90 (m, 3H); 3.00-3.15 (m, 3H); 3.35 (broad s, 3H); 3.45-3.60 (m, 2H); 3.65-3.75 (m, 1H); 6.45 (d, 1H); 6.50 (s, 1H); 6.95 (d, 1H); 7.15 (t, 2H); 7.25-7.35 (m, 2H).

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 hours
  3. customvolatile material was evaporated in vacuo
  4. dissolutionThe thus obtained carboxylic acid chloride was dissolved in dichloromethane (100 ml)
  5. additionadded dropwise to a solution of 4-(4-fluorophenyl)piperidine (19.5 g) and triethylamine (7 ml) in dichloromethane (100 ml) at 0-5° C
  6. additionWater was added
  7. customthe organic phase separated
  8. washwashed with brine
  9. dry with materialdried (anh. MgSO4)
  10. filtrationfiltered
  11. customdichloromethane evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d8765436f22545a1a788be992993b14c
Quelldatensatz
uspto-grants-2004_06
Patentnummer
US06743808B1

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