Tetrahydrofuran → Canagliflozin

HRID 2172701노트

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HRID 2172701 반응식
C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH2:31][C:32]2[S:33][C:34]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:35][CH:36]=2)[CH:25]=1)(=O)C.O1CCCC1.O[Li].O>CO.O>[F:43][C:40]1[CH:41]=[CH:42][C:37]([C:34]2[S:33][C:32]([CH2:31][C:26]3[CH:25]=[C:24]([C@@H:6]4[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]4[OH:4])[CH:29]=[CH:28][C:27]=3[CH3:30])=[CH:36][CH:35]=2)=[CH:38][CH:39]=1

참가 물질

6

반응물 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 25224976(1S)-2,3,4,6-Tetra-O-acetyl-1,5-anhydro-1-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-D-glucitol

생성물 1

HCID 24812758Canagliflozin수율 80.8%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

실험 절차

(1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucitol (5 g) was dissolved in methanol (35 mL) and tetrahydrofuran (25 mL) at room temperature. A solution of LiOH hydrate (192 mg) in water (10 mL) was added dropwise to the mixture for 30 minutes at 20-24° C. After the mixture was stirred for 19 hours at room temperature, the solvent was evaporated in vacuo. The residue was partitioned to ethyl acetate (50 mL) and water (25 mL), stirred for 15 minutes, then the layers were separated. The organic layer was washed with water. The organic layer was dried over Na2SO4, filtered using activated carbon pre-coated filter and evaporated. The resulting residue was dissolved in ethyl acetate (11.1 mL) at 40° C., water (241 mL) was added to the mixture at the same temperature. n-Heptane (5.6 mL) was added to the mixture at 40° C., then the mixture was seeded with a slight amount of (1S)-1,5-anhydro-1-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucitol at same temperature. After stirred for 1 hour at 35° C., n-heptane (2.6 mL) was added slowly to the mixture. The resulting mixture was cooled. The precipitate was filtered and washed with ethyl acetate/n-heptane, then dried to give hemihydrate of (1S)-1,5-anhydro-1-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucitol (2.93 g) as white crystals.

후처리

  1. customat room temperature
  2. customthe solvent was evaporated in vacuo
  3. customThe residue was partitioned to ethyl acetate (50 mL) and water (25 mL)
  4. stirringstirred for 15 minutes
  5. customthe layers were separated
  6. washThe organic layer was washed with water
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe resulting residue was dissolved in ethyl acetate (11.1 mL) at 40° C.
  11. additionwater (241 mL) was added to the mixture at the same temperature
  12. additionn-Heptane (5.6 mL) was added to the mixture at 40° C.
  13. stirringAfter stirred for 1 hour at 35° C.
  14. additionn-heptane (2.6 mL) was added slowly to the mixture
  15. temperatureThe resulting mixture was cooled
  16. filtrationThe precipitate was filtered
  17. washwashed with ethyl acetate/n-heptane
  18. customdried

출처 및 근거

ORD 기록
ord-9391cd7041ba497b93cb4b07c8a068e7
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056850B2

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