Trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester → Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

HRID 1513935노트

반응식

HRID 1513935 반응식
[CH3:1][S:2]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:19][CH:18]=1)=[C:11](OS(C(F)(F)F)(=O)=O)[CH:10]=[CH:9]2)(=[O:4])=[O:3].[F:41][C:42]1[C:43]([S:52][CH3:53])=[C:44](B(O)O)[CH:45]=[C:46]([F:48])[CH:47]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[F:41][C:42]1[C:43]([S:52][CH3:53])=[C:44]([C:11]2[C:12]([C:16](=[O:32])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]4)=[CH:19][CH:18]=3)=[C:13]3[C:8](=[CH:9][CH:10]=2)[CH:7]=[C:6]([O:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:15]=[CH:14]3)[CH:45]=[C:46]([F:48])[CH:47]=1

참가 물질

5

반응물 2

HCID 11628623Trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl esterHCID 575525453,5-Difluoro-2-methylsulfanylphenylboronic acid

생성물 1

HCID 57552531Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester수율 90%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 10340Sodium Carbonate용매

반응 조건

온도
110 °C

실험 절차

Charge a flask with trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (8.8 g, 14.6 mmol) and 3,5-difluoro-2-methylsulfanyl-benzene boronic acid (9.0 g, 42 mmol) and flush with nitrogen. Dissolve solids in degassed dioxane (240 mL). Add 2M sodium carbonate (120 mL) and Pd(PPh3)4 (6.7 g, 5.9 mmol). Plunge into 110° C. oil bath and stir vigorously. After 30 minutes, cool the reaction to room temperature and filter off solids. Partition the filtrate between water and methylene chloride. Wash the organic layer with water twice, dry over sodium sulfate, filter and concentrate. Purify the residue over silica gel, eluting with 1 to 2% methanol in methylene chloride, to yield 8.0 g (90%) of the title compound. LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=3.18 mm (99%); mass spectrum (ion spray): m/z=612.3 (M+H).

후처리

  1. customflush with nitrogen
  2. dissolutionDissolve solids in degassed dioxane (240 mL)
  3. temperaturecool
  4. customthe reaction to room temperature
  5. filtrationfilter off solids
  6. customPartition the filtrate between water and methylene chloride
  7. washWash the organic layer with water twice
  8. dry with materialdry over sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate
  11. customPurify the residue over silica gel
  12. washeluting with 1 to 2% methanol in methylene chloride

출처 및 근거

ORD 기록
ord-1459c4775e2347a6b271b4c6bd987093
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217032B2

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