Cesium carbonate → 4-{[N-((1R)-1-Carbamoyl-3-methyl-butyl)-N-(4-chlorobenzenesulfonyl)amino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 507307Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 507307
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:13]([NH2:15])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>CN(C=O)C>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][N:11]([C@@H:12]([C:13](=[O:14])[NH2:15])[CH2:16][CH:17]([CH3:19])[CH3:18])[S:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)(=[O:9])=[O:10])[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidineHCID 59001058(2R)-2-(4-Chlorobenzenesulfonylamino)-4-methylpentanoic acid amide

Produkt 1

HCID 590010954-{[N-((1R)-1-Carbamoyl-3-methyl-butyl)-N-(4-chlorobenzenesulfonyl)amino]-methyl}-piperidine-1-carboxylic acid tert-butyl esterAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a solution of (2R)-2-(4-chlorobenzenesulfonylamino)-4-methylpentanoic acid amide (4.2 grams, 14 mmol) in DMF (50 mL) was added cesium carbonate (13.6 grams, 417 mmol). To this reaction was added 4-(toluene-4-sulfonyloxymethyl)-piperidine 1-carboxylic acid tert-butyl ester (ref.: Gilissen, C.; Bormans, G.; De Groot, T.; Verbniggen, A. J. Labeled Cmpd. Radiopharm. 1999, 42, 1289; 10.4 g, 282 mmol). The reaction was stirred at 70° C. for 18 h. The reaction was then quenched with sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was collected, washed with brine, dried over MgSO4, and concentrated to a clear oil. The oil was then purified on a Biotage 40S (eluted with 30% EtOAc in hexanes) to afford a white solid (3.0 g, 44%). MS (ESI), (M+H)+ 502.1; 1H NMR (DMSO-d6, 500 MHz) δ 7.86 (dd, 2H, J=2.0, 6.8), 7.65 (dd, 2H, J=2.0, 6.8) 7.37 (br s, 1H), 7.07 (br s, 1H), 4.19 (t, 1H, J=7.6), 3.92 (br s, 2H), 3.35 (dd, 1H, J=15, 6.8), 3.05 (dd, 1H, J=15, 8.1), 1.85 (br s, 1H), 1.50-1.70 (m, 4H), 1.38 (s, 9H), 1.10-1.20 (m, 1H), 0.80-1.00 (m, 3H), 0.82 (d, 6H, J=7.6).

Aufarbeitung

  1. customThe reaction was then quenched with sat. aq. NaHCO3
  2. extractionextracted with EtOAc
  3. customThe organic layer was collected
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to a clear oil
  7. customThe oil was then purified on a Biotage 40S (eluted with 30% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-810b2ec42e2b4b52843bf7aa09495a84
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786122B2

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