Hydrochloric Acid → HCID 178453607, Verbindung

HRID 479272Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 479272
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16](O)=[O:17])[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.COC(Cl)=O.Cl>ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C@H:10]1[CH2:11][CH2:12][C@H:13]([CH2:16][OH:17])[CH2:14][CH2:15]1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 178453624HCID 178453624, Verbindung

Produkt 1

HCID 178453607HCID 178453607, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

A solution of trans-4-(tert-butoxycarbonylamino-methyl)-cyclohexanecarboxylic acid (obtained according to: EP 0614 911 A1) (34.5 g) and triethylamine (28 ml) in dichloromethane (700 ml) is cooled to −70° C. and treated with methylchloroformate (12.9 ml). The reaction mixture is stirred 0.5 h at −70° C. The temperature is allowed to increase to 0° C. and the solution is stirred another 0.5 h until completion of the reaction. The reaction mixture is taken up in ice-cold dichloromethane, washed with an ice-cold 0.5 N HCl solution, a saturated aqueous sodium carbonate solution and water. The organics are dried over sodium sulfate and concentrated to 41.3 g of mixt-anhydride as an oil. This material is taken up in THF and treated at −70° C. with sodium borohydride (5.90 g), followed by absolute methanol (10 ml). The reaction mixture is stirred 15 h at 0° C. and 1 h at ambient temperature to drive the reaction to completion. A 0.5N HCl solution is then carefully added at 0° C., followed by ethyl acetate. The organics are washed with a saturated aqueous sodium carbonate solution, water, dried over sodium sulfate and concentrated. Chromatography on silica gel (A1) yields trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester as a white powder, melting at 88-89° C. Rf (A1) 0.24.

Aufarbeitung

  1. temperatureto increase to 0° C.
  2. stirringthe solution is stirred another 0.5 h until completion of the reaction
  3. washwashed with an ice-cold 0.5 N HCl solution
  4. dry with materialThe organics are dried over sodium sulfate
  5. concentrationconcentrated to 41.3 g of mixt-anhydride as an oil
  6. additiontreated at −70° C. with sodium borohydride (5.90 g)
  7. stirringThe reaction mixture is stirred 15 h at 0° C. and 1 h at ambient temperature
  8. customthe reaction to completion
  9. washThe organics are washed with a saturated aqueous sodium carbonate solution, water
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-2ef078c3b9d548058389737f7b73ff21
Quelldatensatz
uspto-grants-2003_11
Patentnummer
US06645774B1

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