Catecholborane → (S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate

HRID 718380

Reaktionsgleichung

Reaktionsgleichung von HRID 718380
O1C2C=CC=CC=2OB1.[Br:10][C:11]1[C:12]([N:27]2[CH2:30][C:29]([CH3:32])([CH3:31])[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[CH2:30][C:29]([CH3:32])([CH3:31])[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 118307716Isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

Produkt 1

HCID 118307698(S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetateAusbeute 61,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

The 1.5 mL of benzo[d][1,3,2]dioxaborole (751 mg, 6.26 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (1.6 g, 4.17 mmol) and 1.25 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (347 mg, 1.25 mmol) in toluene (40 mL) at −60° C. and allowed to warm to −15° C. before being placed in the freezer overnight. The reaction was quenched with 1M Na2CO3 (15 mL), diluted with EtOAc, and stirred for 20 min. The organic layer was washed with brine and dried (Na2SO4). The crude product was charged (DCM) to an 80 g ISCO silica gel cartridge and gradient elution (5-35% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 987 mg (61%). 1H NMR (500 MHz, DMSO-d6) δ 5.16 (s, 1H), 4.97-4.92 (m, 1H), 4.13 (d, J=7.7 Hz, 2H), 4.04 (d, J=7.7 Hz, 2H), 2.42 (s, 3H), 2.21 (s, 3H), 1.22 (s, 6H), 1.17 (d, J=6.2 Hz, 3H), 1.12 (d, J=6.2 Hz, 3H). UPLC (M+H)=387.2.

Aufarbeitung

  1. custombefore being placed in the freezer overnight
  2. customThe reaction was quenched with 1M Na2CO3 (15 mL)
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. additionThe crude product was charged (DCM)
  7. washto an 80 g ISCO silica gel cartridge and gradient elution (5-35% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-53236679e46d46a0aade26d6e30b238e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193720B2

Verknüpfte Notizen

Wird geladen…