Catecholborane → (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-hydroxyacetate

HRID 718387

Reaktionsgleichung

Reaktionsgleichung von HRID 718387
O1C2C=CC=CC=2OB1.[Br:10][C:11]1[C:12]([N:27]2[CH2:32][CH2:31][CH:30]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:29][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[CH2:32][CH2:31][CH:30]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:29][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 118307748Isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-oxoacetate

Produkt 1

HCID 118307826(S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-hydroxyacetateAusbeute 76,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

The 2.2 mL of benzo[d][1,3,2]dioxaborole (1.22 g, 10.2 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-oxoacetate (2.6 g, 5.66 mmol) and 1.7 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (471 mg, 1.7 mmol) in toluene (50 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 (MgSO4). The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient elution (5-45% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-hydroxyacetate 2.0 g (71%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.34-7.29 (m, 4H), 7.22-7.19 (m, 1H), 5.95 (s, 1H), 4.99-4.94 (m, 1H), 3.78-3.75 (m, 1H), 3.51-3.47 (m, 1H), 3.04-3.02 (m, 1H), 2.90-2.87 (m, 1H), 2.66-2.61 (m, 1H), 2.54 (s, 3H), 2.41 (s, 3H), 1.87-1.72 (m, 4H), 1.14 (d, J=6.2 Hz, 3H), 1.07 (d, J=5.9 Hz, 3H). UPLC (M+H)=463.2.

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 (MgSO4)
  6. additionThe crude product was charged (DCM)
  7. washto a 80 g ISCO silica gel cartridge and gradient elution (5-45% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-6ec848af442045069e1791ceed42443e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193720B2

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