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

HRID 718390

反応式

HRID 718390 の反応式
O1C2C=CC=CC=2OB1.[Br:10][C:11]1[C:12]([N:27]2[CH2:32][CH2:31][CH:30]([C:33]3[O:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[N: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[O:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[N: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]

参加物

5

反応物 3

HCID 67506CatecholboraneHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 118307821Isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

生成物 1

HCID 118307876(S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate収率 58%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-15 °C

実験手順

The 1.6 mL of benzo[d][1,3,2]dioxaborole (416 mg, 3.47 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (950 mg, 1.93 mmol) and 0.6 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (160 mg, 0.58 mmol) in toluene (20 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 (5 mL), diluted with EtOAc, and stirred for 20 min. The organic layer was washed with brine and dried (MgSO4). The crude product was filtered, and charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-60% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 550 mg (58%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 5.98/5.87 (s, 1H), 4.95-4.92 (m, 1H), 3.75-3.71 (m, 1H), 3.08-3.01 (m, 3H), 2.88-2.86 (m, 1H), 2.54 (s, 3H), 2.39 (s, 3H), 2.06-2.00 (m, 3H), 1.90-1.83 (m, 2H), 1.27 (d, J=6.6 Hz, 6H), 1.14 (d, J=5.9 Hz, 3H), 1.08 (d, J=5.9 Hz, 3H). UPLC (M+H)=497.2.

後処理

  1. custombefore being placed in the freezer overnight
  2. customThe reaction was quenched with 1M Na2CO3 (5 mL)
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationThe crude product was filtered
  7. additioncharged (DCM)
  8. washto a 40 g ISCO silica gel cartridge and gradient elution (5-60% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-bd635da1f0314e1b995287f0c2c5dcfd
出典データセット
uspto-grants-2015_11
特許番号
US09193720B2

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