Acetic Acid → 1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazol-4-ol

HRID 1269932노트

반응식

HRID 1269932 반응식
C([Li])CCC.CCCCCC.Br[C:13]1[C:21]([O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[N:16][N:17]2[CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][O:30]1.C[O:36]B(OC)OC.C(O)(=O)C.OO.S([O-])(O)=O.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1.O>[O:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH:29]1[N:17]1[C:18]2[CH:19]=[CH:20][C:21]([O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[C:13]([OH:36])[C:14]=2[CH:15]=[N:16]1

참가 물질

10

반응물 7

HCID 176Acetic AcidHCID 784Hydrogen Peroxide2회HCID 8470Trimethyl borateHCID 516892Sodium BicarbonateHCID 23665763Sodium BisulfiteHCID 694325024-bromo-1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazoleHCID 178418244HCID 178418244, 화합물

생성물 1

HCID 1363517781-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazol-4-ol수율 59.8%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

실험 절차

Under a nitrogen atmosphere, a 1.57M-n-butyllithium/hexane solution (12.00 ml, 0.0189 mol) was added dropwise to a solution of the 4-bromo-1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazole (6.0 g, 0.0157 mol) obtained in Example 607 in tetrahydrofuran (120 ml) at −78° C. over a period of 15 minutes. After 30 minutes, a solution of trimethoxyborane (2.65 ml, 0.0236 mol) in tetrahydrofuran (30 ml) was added dropwise thereto over a period of 5 minutes and the resulting mixture was slowly heated. After 15 hours, acetic acid (1.98 ml, 0.0346 mol) was added thereto. After 15 minutes, a solution of 30%-aqueous hydrogen peroxide solution (4.46 ml, 0.0393 mol) in tetrahydrofuran (20 ml) was added dropwise thereto over a period of 10 minutes, and the resulting mixture was slowly heated to room temperature. After 8.5 hours, a 30%-aqueous hydrogen peroxide solution (4.72 mmol) was further added thereto. After 15 hours, a 10%-aqueous sodium hydrogensulfite solution and a saturated aqueous sodium hydrogencarbonate solution were added thereto, and the resulting mixture was poured into water and extracted with ethyl acetate. The extract solution was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate). The residue purified was concentrated under reduced pressure and the resulting residue was washed with hexane by repulping to obtain 1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazol-4-ol (2.9892 g, 42%).

후처리

  1. waitover a period of 5 minutes
  2. temperaturethe resulting mixture was slowly heated
  3. waitAfter 15 hours
  4. waitAfter 15 minutes
  5. waitover a period of 10 minutes
  6. waitAfter 8.5 hours
  7. waitAfter 15 hours
  8. extractionextracted with ethyl acetate
  9. concentrationThe extract solution was concentrated under reduced pressure
  10. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
  11. customThe residue purified
  12. concentrationwas concentrated under reduced pressure
  13. washthe resulting residue was washed with hexane

출처 및 근거

ORD 기록
ord-486160f857464ae89b624300daf7b4a0
출처 데이터셋
uspto-grants-2007_04
특허 번호
US07199147B2

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