Dimethylformamide → (E)-methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-phenylacrylate

HRID 563402Notes

Reaction equation

C[C:2](P(OC)(O)=O)([C:4]([O-:6])=[O:5])C.[Na].[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[C:23](=[CH:24][C:25]([C:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=O)=[CH:26][CH:27]=3)[CH:22]=[N:21]2)=[CH:16][CH:15]=1.[CH3:37]N(C=O)C>C1COCC1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[C:23](=[CH:24][C:25](/[C:29](/[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:2]/[C:4]([O:6][CH3:37])=[O:5])=[CH:26][CH:27]=3)[CH:22]=[N:21]2)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Trimethylphosphonoacetate (2.4 g, 13.4 mmol) was dissolved in 15 mL anhydrous DMF and treated with sodium hexadimethylsilazane (13.4 mmol, 1 M in THF). (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanone (1.63 g, 5.16 mmol) was added and the reaction was heated to 85° C. for 16 hours. The following day, the cooled reaction was extracted from brine using ether×3 and the combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel using 25% EtOAc in hexanes to give 1.74 g (91%) of (E)-methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-phenylacrylate as a clear oil. MS found: (M+H)+=373.

Workup

customThe following day, the cooled reaction
extractionwas extracted from brine
dry with materialthe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was chromatographed on silica gel using 25% EtOAc in hexanes

Sources & evidence

ORD record: ord-7239e854cb5047679ec6649465c94480
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067447B2

Reaction notes

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