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

HRID 718380

반응식

HRID 718380 반응식
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]

참가 물질

5

반응물 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

생성물 1

HCID 118307698(S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate수율 61.4%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
-15 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-53236679e46d46a0aade26d6e30b238e
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193720B2

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