Diisopropylamine → HCID 18374658, Verbindung

HRID 2301189Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2301189
C(NC(C)C)(C)C.C([Li])CCC.[O:13]=[C:14]1[CH2:18][CH2:17][C:16]2([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[O:15]1.[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][CH:33]=1>C1COCC1>[O:13]=[C:14]1[CH:18]([CH2:36][C:35]2[CH:38]=[CH:39][C:32]([F:31])=[CH:33][CH:34]=2)[CH2:17][C:16]2([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[O:15]1

Komponenten

6

Edukt 4

HCID 7912DiisopropylamineHCID 680214-Fluorobenzyl bromideHCID 18374740tert-Butyl 2-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 18374658HCID 18374658, VerbindungAusbeute 70,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of diisopropyl amine (0.36 mL, 2.6 mmol) in 7.5 mL dry THF was cooled to −78° C. and n-butyllithium (1.5 mL, 1.6 M in hexane, 2.4 mmol) was added. The mixture was warmed to 0° C. for 15 min then recooled to −78° C. A solution of 2-oxo-8-(t-Butoxycarbonyl)-8-aza-1-oxaspiro[4.5]decane (510 mg, 2.0 mmol, from Step B) in 2 mL THF was added dropwise. After 30 min at −78° C. 4-fluorobenzyl bromide (0.32 mL, 2.6 mmol) was added and after 30 min the mixture was warmed to room temperature and quenched with sat'd ammonium chloride. The mixture was extracted with ethyl acetate and the organic portion was dried over sodium sulfate and concentrated. Flash chromatography (3/1 hexane/EtOAc) afforded 510 mg (70%) of the desired product. 1H NMR (400 MHz, CDCl3). δ 1.44 (s, 9H), 1.51-1.81 (5H), 2.03-2.19 (m, 1H), 2.76-2.81 (dd, 1H), 2.99-3.04 (m, 1H), 3.18-3.3 (m, 3H), 3.72-3.81 (m, 2H), 6.97-7.03 (m, 2H), 7.11-7.18 (m, 2H). The lactone was separated into its enantiomers by semiprep chiral HPLC (chiralpak AD, 9/1 hexane/IPA→8/1 hexane/IPA) to afford the two enantiomers (enantiomer A, 92% ee and enantiomer B, 73% ee). The two enantiomers were converted to the spiro tetrahydrofuran derivatives as described below for enantiomer B.

Aufarbeitung

  1. customthen recooled to −78° C
  2. temperaturewas warmed to room temperature
  3. customquenched with sat'd ammonium chloride
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialthe organic portion was dried over sodium sulfate
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-a0c77009bbdf4cd59b84d2f8f67d448c
Quelldatensatz
uspto-grants-2002_12
Patentnummer
US06498161B1

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