3,4-dihydro-2H-pyran → Ethyl 6-(tert-butyldiphenylsilyloxy)-1-(tetrahydro-2H-pyran-2-yl)indazole-3-carboxylate

HRID 1873953Notes

Reaction equation

HRID 1873953 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:13]=2)[NH:8][N:7]=1)=[O:5])[CH3:2].[O:33]1[CH:38]=[CH:37][CH2:36][CH2:35][CH2:34]1.O.C1(C)C(S(O)(=O)=O)=CC=CC=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][Si:16]([C:29]([CH3:31])([CH3:30])[CH3:32])([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:13]=2)[N:8]([CH:34]2[CH2:35][CH2:36][CH2:37][CH2:38][O:33]2)[N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 124969952-Methylbenzenesulfonic acid hydrateHCID 59370747Ethyl6-tert-butyldiphenylsilyloxyindazole-3-carboxylate

Product 1

HCID 59370763Ethyl 6-(tert-butyldiphenylsilyloxy)-1-(tetrahydro-2H-pyran-2-yl)indazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl6-tert-butyldiphenylsilyloxyindazole-3-carboxylate (1.461 g) which can be prepared according to the method described in Reference example 18, etc. was dissolved in toluene (16.5 mL; manufactured by Wako Pure Chemical Industries, Ltd.), added with 3,4-dihydro-2H-pyran (0.6 mL; manufactured by Tokyo Chemical Industry, Co., Ltd.) and toluene sulfonic acid-monohydrate (0.1293 g), followed by stirring overnight at 60° C. under nitrogen atmosphere. The reaction solution was poured to a saturated aqueous solution of sodium hydrogen carbonate and extracted once with ethyl acetate. The organic layer was washed twice with water and once with brine and dried over anhydrous magnesium sulfate. After the solvent was evaporated under reduced pressure, the residue was purified by column chromatography “COLUMN-A”; n-hexane:ethyl acetate=96:4→75:25) to obtain the title compound (1.334 g).

Workup

  1. extractionextracted once with ethyl acetate
  2. washThe organic layer was washed twice with water and once with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customAfter the solvent was evaporated under reduced pressure
  5. customthe residue was purified by column chromatography “COLUMN-A”

Sources & evidence

ORD record
ord-3e8e9e2803e84802b3d953943386a3b1
Source dataset
uspto-grants-2012_11
Patent number
US08304443B2

Reaction notes

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