3,4-dihydro-2H-pyran → 6-Chloro-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxylic acid methyl ester

HRID 1827453Notes

Reaction equation

HRID 1827453 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][N:6]=1)=[O:4].[O:15]1[CH:20]=[CH:19][CH2:18][CH2:17][CH2:16]1.C([O-])(O)=O.[Na+]>CC#N.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[N:7]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][O:15]2)[N:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 23577858Methyl 6-chloro-1H-indazole-3-carboxylate

Product 1

HCID 235778596-Chloro-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxylic acid methyl esterYield 66%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a slurry of 6-Chloro-1H-indazole-3-carboxylic acid methyl ester (8.3 g, 39.5 mmol) in MeCN (200 mL) was added 3,4-Dihydro-2H-pyran (5.4 mL, 59.3 mmol) and p-toluenesulfonic acid (237 mg, 1.25 mmol). After letting the reaction stir for 10 minutes, saturated NaHCO3 (1 mL) was added and the solvent was removed by rotary evaporation to a volume of 100 mL. The mixture was diluted with EtOAc and washed with water (50 mL) and then with saturated NaCl (50 mL). The organic layer was then dried over Na2SO4. After the solids were removed by filtration, the organic layer was concentrated to an oil by rotary evaporation. The product was precipitated from the oil using hexanes to yield the desired product (7.667 g, 66% yield).

Workup

  1. customthe solvent was removed by rotary evaporation to a volume of 100 mL
  2. additionThe mixture was diluted with EtOAc
  3. washwashed with water (50 mL)
  4. dry with materialThe organic layer was then dried over Na2SO4
  5. customAfter the solids were removed by filtration
  6. concentrationthe organic layer was concentrated to an oil by rotary evaporation
  7. customThe product was precipitated from the oil

Sources & evidence

ORD record
ord-07416bc9095b4061be3f1f53fed8c6e3
Source dataset
uspto-grants-2006_05
Patent number
US07053107B2

Reaction notes

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