Catecholborane → HCID 118307798, Verbindung

HRID 718374

Reaktionsgleichung

Reaktionsgleichung von HRID 718374
O1C2C=CC=CC=2OB1.[Br:10][C:11]1[C:12]([N:27]2[CH2:31][CH2:30][CH:29]([CH:32]3[CH2:34][CH2:33]3)[CH2:28]2)=[C:13]([C:19](=[O:26])[C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])[C:14]([CH3:18])=[N:15][C:16]=1[CH3:17].CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1>C1(C)C=CC=CC=1>[Br:10][C:11]1[C:12]([N:27]2[CH2:31][CH2:30][CH:29]([CH:32]3[CH2:34][CH2:33]3)[CH2:28]2)=[C:13]([C@H:19]([OH:26])[C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])[C:14]([CH3:18])=[N:15][C:16]=1[CH3:17]

Komponenten

5

Edukt 3

HCID 67506CatecholboraneHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 118307755Isopropyl 2-(5-bromo-4-(3-cyclopropylpyrrolidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

Produkt 1

HCID 118307798HCID 118307798, VerbindungAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
-50 °C

Versuchsvorschrift

The benzo[d][1,3,2]dioxaborole (0.66 mL, 2.68 mmol; 50% soln in toluene) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(3-cyclopropylpyrrolidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (730 mg, 1.78 mmol) and 0.6 ml, of 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (148 mg, 0.54 mmol) in toluene (18 mL) cooled to −50° C. The reaction was allowed to slowly warm to −15° C. and placed in the freezer for 18 h before being quenched with 1M Na2CO3 (5 mL) and stirred for 20 min. The organic layer was washed with brine and dried (MgSO4). The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-50% EtOAc/hexanes) using an Isolera chromatography station gave (2S)-isopropyl 2-(5-bromo-4-(3-cyclopropylpyrrolidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 540 mg (74%) as a mixture of diastereomers; major isomer. 1H NMR (500 MHz, DMSO-d6) δ 5.52 (s, 1H), 4.96-4.89 (m, 1H), 3.40-3.35 (m, 2H), 3.17-3.09 (m, 1H), 2.94-2.90 (m, 1H), 2.53 (s, 3H), 2.40 (s, 3H), 2.03 (br. s., 1H), 1.82-1.74 (m, 2H), 1.17-1.08 (m, 6H), 0.76-0.75 (m, 1H), 0.43-0.41 (m, 2H), 0.15-0.14 (m, 2H). UPLC (M+H)=413.2.

Aufarbeitung

  1. temperatureto slowly warm to −15° C.
  2. custombefore being quenched with 1M Na2CO3 (5 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. additionThe crude product was charged (DCM)
  6. washto a 40 g ISCO silica gel cartridge and gradient elution (5-50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e83d3e3a594a4fa8b1460a80cea49efd
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193720B2

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