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

HRID 718383

反応式

HRID 718383 の反応式
O1C2C=CC=CC=2OB1.[Br:10][C:11]1[C:12]([N:27]2[CH2:30][CH:29]([CH:31]([CH3:33])[CH3:32])[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][CH:29]([CH:31]([CH3:33])[CH3:32])[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 118307786Isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate

生成物 1

HCID 118307805(S)-isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate収率 71%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-15 °C

実験手順

The 0.7 mL of benzo[d][1,3,2]dioxaborole (396 mg, 3.3 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (875 mg, 2.2 mmol) and 0.66 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (183 mg, 0.66 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 charged (DCM) to a 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-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate 621 mg (71%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 5.19 (d, J=4.4 Hz, 1H), 4.96-4.92 (m, 1H), 4.50 (t, J=8.1 Hz, 1H), 4.39 (t, J=8.4 Hz, 1H), 4.07 (t, J=7.0 Hz, 1H), 3.97 (t, J=7.3 Hz, 1H), 2.42 (s, 3H), 2.21 (s, 3H), 2.21-2.17 (m, 1H), 1.73-1.67 (m, 1H), 1.17 (d, J=6.2 Hz, 3H), 1.12 (d, J=6.2 Hz, 3H), 0.83 (d, J=6.6 Hz, 6H). UPLC (M+H)=401.3.

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 80 g ISCO silica gel cartridge and gradient elution (5-35% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-5a7d88889fcf4e7baddc2a5083805b9a
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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