Dimethyl Succinate → 2-(7-methyl-1H-indazol-5-ylmethylene)-succinic acid 1-methyl ester

HRID 2099740Notes

Reaction equation

[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[C:7]2C=O.C[O:14][C:15]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])=[O:16].[CH3:23]C(C)([O-])C.[K+]>C(O)(C)(C)C>[CH3:22][O:21][C:19](=[O:20])[C:18](=[CH:23][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([CH3:1])[CH:3]=1)[NH:9][N:8]=[CH:7]2)[CH2:17][C:15]([OH:14])=[O:16]

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of 7-methyl indazole aldehyde (0.2619 g, 1.64 mmol) and DBE-4 dibasic ester (dimethyl succinate) (0.32 mL, 2.45 mmol) in t-butanol (20 mL) was added potassium t-butoxide (0.4036 g, 3.60 mmol). The reaction mixture was heated at 50° C. for 2 h under nitrogen. After a further 16 h at room temperature, the solvent was removed in vacuo and the residue was taken up in water (100 mL) and extracted with ethyl acetate (3×50 mL). The aqueous layer was acidified with 1N hydrochloric acid to pH 3˜4 and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate solution was dried and concentrated in vacuo to give the crude product as a yellow solid (99%, cis/trans isomer approximately 40:60). The crude mixture was carried to next step without further purification. Mass spec.: 275 (MH)+.

Workup

customthe solvent was removed in vacuo
extractionextracted with ethyl acetate (3×50 mL)
extractionextracted with ethyl acetate (3×50 mL)
dry with materialThe combined ethyl acetate solution was dried
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-80c3ef5fdf804f79b773e8d6a0f5a76d
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07569578B2

Reaction notes

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