Methyl isobutyrate → 1,1-Dimethylethyl (2R,6S)-4-({4-[1,1-dimethyl-2-(methyloxy)-2-oxoethyl]phenyl}methyl)-2,6-dimethyl-1-piperazinecarboxylate

HRID 43354

Reaktionsgleichung

Reaktionsgleichung von HRID 43354
[CH3:1][CH:2]([CH3:7])[C:3]([O:5][CH3:6])=[O:4].C1([N-]C2CCCCC2)CCCCC1.[Li+].Br[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]2[CH2:35][C@H:34]([CH3:36])[N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:32]([CH3:44])[CH2:31]2)=[CH:25][CH:24]=1>C1(C)C=CC=CC=1.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[CH3:1][C:2]([C:23]1[CH:24]=[CH:25][C:26]([CH2:29][N:30]2[CH2:35][C@H:34]([CH3:36])[N:33]([C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[C@H:32]([CH3:44])[CH2:31]2)=[CH:27][CH:28]=1)([CH3:7])[C:3]([O:5][CH3:6])=[O:4]

Komponenten

7

Edukt 3

HCID 11039Methyl isobutyrateHCID 10932176Lithium dicyclohexylamideHCID 252240971,1-Dimethylethyl (2R,6S)-4-[(4-bromophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylate

Produkt 1

HCID 252242061,1-Dimethylethyl (2R,6S)-4-({4-[1,1-dimethyl-2-(methyloxy)-2-oxoethyl]phenyl}methyl)-2,6-dimethyl-1-piperazinecarboxylateAusbeute 65,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83681Tris(1,1-dimethylethyl)phosphineKatalysatorHCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladiumKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A solution of methyl 2-methylpropanoate (188 ul, 1.64 mmol) in toluene (3 ml) was added to lithium dicyclohexylamide (362 mg, 1.93 mmol) under glove bag conditions. The suspension was stirred for 10 mins then added to a mixture of D43 (570 mg, 1.49 mmol) and bis(dibenzylideneacetone) palladium (0) (43 mg, 0.074 mmol). Tri(tert-butyl)phosphine (18 ul, 0.074 mmol) was added and the reaction mixture stirred at room temperature overnight. The solvent was removed in vacuo and chromatography eluting with 0-90% EtOAc/petroleum ether gave the title compound as a yellow oil (395 mg). δH (CDCl3, 250 MHz) 7.29 (4H, m), 4.07 (2H, m), 3.66 (3H, s), 3.46 (2H, s), 2.61 (2H, m), 2.12 (2H, dd), 1.58 (6H, s), 1.46 (9H, s), 1.29 (6H, d). MS (ES): MH+ 405.

Aufarbeitung

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. customThe solvent was removed in vacuo and chromatography
  3. washeluting with 0-90% EtOAc/petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-c5561e98662a4bdd91f7af42e78611f5
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536182B2

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