2-Hydrazinoethanol → methyl 1-(2-hydroxyethyl)-1H-indazole-7-carboxylate

HRID 2369934Notes

Reaction equation

HRID 2369934 reaction equation
F[C:2]1[C:11]([CH:12]=O)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[OH:14][CH2:15][CH2:16][NH:17][NH2:18]>CO>[OH:14][CH2:15][CH2:16][N:17]1[C:2]2[C:11](=[CH:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])[CH:12]=[N:18]1

Participants

4

Reactant 2

HCID 80172-HydrazinoethanolHCID 57423810Methyl 2-fluoro-3-formylbenzoate

Product 1

HCID 66899478methyl 1-(2-hydroxyethyl)-1H-indazole-7-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl 2-fluoro-3-formylbenzoate (3.6 g, 19.9 mmol) from Step C above and hydroxy ethyl hydrazine (1.5 g, 19.9 mmol) in MeOH (16 mL) was irradiated with microwaves at 150° C. for 1.5 h. The reaction mixture was cooled and partitioned between H2O and ethyl acetate. The aqueous phase was extracted with additional ethyl acetate and then the combined organic extracts were dried (Na2SO4) filtered, concentrated and purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate) to afford methyl 1-(2-hydroxyethyl)-1H-indazole-7-carboxylate as a yellow solid (2.83 g, 65%): 1H NMR (500 MHz, CDCl3) δ 8.13 (s, 1H), 7.99 (d, J=7.5 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H); 7.18 (t, J=8.5 Hz, 1H), 4.84 (t, J=5.0 Hz, 2H), 4.13-4.07 (m, 2H), 3.99 (s, 3H), 3.20-3.10 (m, 1H).

Workup

  1. customwas irradiated with microwaves at 150° C. for 1.5 h
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between H2O and ethyl acetate
  4. extractionThe aqueous phase was extracted with additional ethyl acetate
  5. dry with materialthe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-640bd481acb6430b847e65da0319016e
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

Loading…