Levoglucosan → Canagliflozin

HRID 520850

반응식

HRID 520850 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([CH:20]=1)[CH2:7][C:8]1[S:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[CH:11][CH:12]=1.C([Li])CCC.[Cl-].C([Al+]CC(C)C)C(C)C.[C@@H:37]12[O:47][CH2:46][C@@H:44]([O:45]1)[C@@H:42]([OH:43])[C@H:40]([OH:41])[C@H:38]2[OH:39].[H-].C([Al+]CC(C)C)C(C)C.[Al]>CC1CCCO1.C1(OC)C=CC=CC=1>[CH3:21][C:5]1[CH:4]=[CH:3][C:2]([C@@H:37]2[O:45][C@H:44]([CH2:46][OH:47])[C@@H:42]([OH:43])[C@H:40]([OH:41])[C@H:38]2[OH:39])=[CH:20][C:6]=1[CH2:7][C:8]1[S:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[CH:11][CH:12]=1

참가 물질

9

반응물 6

HCID 2724705LevoglucosanHCID 5359268AluminumHCID 16686353Diisobutyl aluminium chlorideHCID 21225700DiisobutylaluminumhydrideHCID 469304322-(5-Bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiopheneHCID 178418339Butyllithium

생성물 1

HCID 24812758Canagliflozin수율 42%

시약·촉매·용매 2

HCID 73012-Methyltetrahydrofuran용매HCID 7519Anisole용매

실험 절차

To a solution of 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (796 mg, 2.2 mmol) in 2-methyltetrahydrofuran (20 mL) was added dropwise n-butyl lithium (1.63 mL, 2.6 mmol, 1.6 M in hexane) at −76° C. and was then stirred for 30 min. Diisobutylaluminum chloride (4.4 mL, 3.5 mmol, 0.8 M in n-heptane) was added and the mixture was stirred for 1 hour and then warmed to ambient temperature and was stirred overnight. To a suspension of 1,6-anhydro-β-D-glucopyranose (648 mg, 4.0 mmol) in anisole (10 mL) at 0° C. was added dropwise diisobutylaluminum hydride (12 mL, 12 mmol, 1.0 M in toluene) and was then stirred at ambient temperature overnight. This solution was then added to the above prepared aluminum mixture via syringe. The mixture was distilled (external bath temperature was 158° C.) to remove the low-boiling solvents. To the remaining mixture was added anisole (10 mL) and the mixture was heated (external bath temperature was 158° C.) for 22 hours at which time HPLC assay analysis indicated a 42% yield of 1-C-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-β-D-glucopyranoside.

후처리

  1. stirringthe mixture was stirred for 1 hour
  2. stirringwas stirred overnight
  3. stirringwas then stirred at ambient temperature overnight
  4. additionThis solution was then added to the
  5. distillationThe mixture was distilled (external bath temperature was 158° C.)
  6. customto remove the low-boiling solvents
  7. additionTo the remaining mixture was added anisole (10 mL)
  8. temperaturethe mixture was heated (external bath temperature was 158° C.) for 22 hours at which time HPLC assay analysis

출처 및 근거

ORD 기록
ord-332bc69448c4424397fb4152f1f98397
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328100B2

연결된 노트

불러오는 중…