Hexamethylphosphoramide → 5-(2-Benzyloxy-ethyl)-2-oxo-cyclohexanecarboxylic acid methyl ester

HRID 9294

Reaktionsgleichung

Reaktionsgleichung von HRID 9294
[Li+].CC([N-]C(C)C)C.[CH2:9]([O:16][CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN(P(N(C)C)(N(C)C)=O)C.C([C:39]([O:41][CH3:42])=[O:40])#N>C1COCC1>[CH3:42][O:41][C:39]([CH:23]1[CH2:24][CH:19]([CH2:18][CH2:17][O:16][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:20][CH2:21][C:22]1=[O:25])=[O:40]

Komponenten

6

Edukt 4

HCID 12679HexamethylphosphoramideHCID 28660Carbonocyanidic acid, methyl esterHCID 2724682Lithium diisopropylamideHCID 218796054-(2-Benzyloxyethyl)cyclohexanone

Produkt 1

HCID 574432435-(2-Benzyloxy-ethyl)-2-oxo-cyclohexanecarboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of LDA (33 ml, 1.5 M in Et2O) in THF (50 mL) at −78° C. was treated with 4-(2-benzyloxy-ethyl)-cyclohexanone (9.5 g, 40.2 mmol). The mixture was warmed to 0° C. over 30 m before re-cooling to −78° C. and adding HMPA (7 mL). Methyl cyanoformate (4.1 mL, 85 mmol) was added and the mixture was stirred for 15 m before aqueous quench and work-up. The product was purified by chromatography on SiO2 with 10% EtOAc:Hx. 5-(2-Benzyloxy-ethyl)-2-oxo-cyclohexanecarboxylic acid methyl ester was isolated, 5.8 g (49%) and reduced with an equivalent of NaBH4 in MeOH at −10° C. to provide the alcohol (Intermediate R2). Intermediate R2 was purified by chromatography on SiO2 with 30 to 50% EtOAC:Hx. (˜90% yield).

Aufarbeitung

  1. temperaturebefore re-cooling to −78° C.
  2. custombefore aqueous quench
  3. customThe product was purified by chromatography on SiO2 with 10% EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-36c0fb0cef9b4fd690399403bca865cf
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091232B2

Verknüpfte Notizen

Wird geladen…