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

HRID 1269932Notes

Reaction equation

HRID 1269932 reaction equation
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

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 784Hydrogen Peroxide2×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, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-486160f857464ae89b624300daf7b4a0
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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