Hydrochloric Acid → 1h-Indazole-3-carboxylic acid,4,5,6,7-tetrahydro-1-(phenylmethyl)-,ethyl ester

HRID 343121Notes

Reaction equation

HRID 343121 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[NH:8][N:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N:8]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 6624328ethyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate

Product 1

HCID 105650011h-Indazole-3-carboxylic acid,4,5,6,7-tetrahydro-1-(phenylmethyl)-,ethyl esterYield 35.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 2.0 g (10.30 mmol) of 4,5,6,7-Tetrahydro-1H-indazole-3-carboxylic acid ethyl ester (Ainsworth, C. J. Am. Chem. Soc. 1957, 79, 5242) in 50 mL of DMF is added 1.85 g (13.838 mmol, 1.3 equiv) of K2CO3, followed by 1.35 mL (11.33 mmol, 1.1 equiv) of benzyl bromide. The reaction mixture is stirred 15 min at RT then heated at 60° C. for 16 h. The reaction is cooled to RT, poured into 100 mL 1N HCl, and extracted with Et2O (2×100 mL). The organic layers were washed with H2O (2×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using a gradient elution of hexane/EtOAc 6/1 to 3/1 afforded 1.05 g of 4,5,6,7-Tetrahydro-1-Benzyl-1H-indazole-3-carboxylic acid ethyl ester as a yellow oil which later solidified: 1H NMR (CDCl3, 300 MHz) δ7.37-7.23 (m, 3H), 7.13 (m, 2H), 5.31 (s, 2H), 4.39 (q, 2H, J=7.2), 2.74 (m, 2H), 2.40 (m, 2H), 1.72 (m, 4H), 1.39 (t, 3H, J=7.2).

Workup

  1. temperaturethen heated at 60° C. for 16 h
  2. temperatureThe reaction is cooled to RT
  3. extractionextracted with Et2O (2×100 mL)
  4. washThe organic layers were washed with H2O (2×100 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customPurification of the crude material by silica gel flash column chromatography
  8. washa gradient elution of hexane/EtOAc 6/1 to 3/1

Sources & evidence

ORD record
ord-5ef68fe91e8c4b1c9b90e5095686d629
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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