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

HRID 1269932ノート

反応式

HRID 1269932 の反応式
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

参加物

10

反応物 7

HCID 176Acetic AcidHCID 784Hydrogen Peroxide2 回HCID 8470Trimethyl borateHCID 516892Sodium BicarbonateHCID 23665763Sodium BisulfiteHCID 694325024-bromo-1-tetrahydro-2H-pyran-2-yl-5-(tetrahydro-2H-pyran-2-yloxy)-1H-indazoleHCID 178418244HCID 178418244、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-486160f857464ae89b624300daf7b4a0
出典データセット
uspto-grants-2007_04
特許番号
US07199147B2

反応ノート

読み込み中…