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

HRID 718377

反応式

HRID 718377 の反応式
O1C2C=CC=CC=2OB1.[Br:10][C:11]1[C:12]([N:27]2[CH2:30][C:29]([F:32])([F: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[CH2:28][C:29]([F:32])([F:31])[CH2:30]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 118307859Isopropyl 2-(5-bromo-4-(3,3-difluoroazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

生成物 1

HCID 118307708(S)-isopropyl 2-(5-bromo-4-(3,3-difluoroazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate収率 51.4%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-15 °C

実験手順

The 0.33 mL of benzo[d][1,3,2]dioxaborole (166 mg, 1.38 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(3,3-difluoroazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (360 mg, 0.920 mmol) and 0.28 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (77 mg, 0.28 mmol) in toluene (10 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 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-(3,3-difluoroazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 186 mg (51%). 1H NMR (500 MHz, DMSO-d6) δ 5.24 (s, 1H), 4.97-4.94 (m, 1H), 4.74-4.71 (m, 2H), 4.54-4.51 (m, 2H), 2.50 (s, 3H), 2.33 (s, 3H), 1.19 (d, J=5.9 Hz, 3H), 1.13 (d, J=5.9 Hz, 3H). LCMS (M+H)=395.1.

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. additionThe crude product was charged (DCM)
  7. 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-7e0fdd39bb3249319f7a843a6e863d90
出典データセット
uspto-grants-2015_11
特許番号
US09193720B2

関連ノート

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