Ammonium Chloride → [1,1′-Biphenyl]-4-carboxylic acid, 2′,6′-difluoro-3′-nitro-, ethyl ester

HRID 522508Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[Li+].[Cl-].I[C:15]1[CH:25]=[CH:24][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=1.[NH4+].[Cl-]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:1][C:2]1[C:3]([N+:9]([O-:11])=[O:10])=[CH:4][CH:5]=[C:6]([F:8])[C:7]=1[C:15]1[CH:25]=[CH:24][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 25 °C

Procedure

2,4-Difluoro-1-nitrobenzene 15 (159 mg, 1.0 mmol) in THF (2 mL) was added to a solution of TMPZnCl.LiCl (2) (1.3 M in THF, 0.85 mL, 1.1 mmol) at 25° C. and the reaction mixture was then stirred at this temperature for 45 min according to TP 2. Pd(dba)2 (17 mg, 3 mol %) and P(o-furyl)3 (14 mg, 6 mol %) dissolved in THF (2 mL), followed by the addition of ethyl 4-iodobenzoate (359 g, 1.3 mmol), were then transferred via cannula at -20° C. The resulting mixture was allowed to warm up slowly to 25° C. overnight. The reaction mixture was then quenchend with a sat. aq. NH4Cl solution (20 mL), extracted with diethyl ether (3×50 mL) and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash-chromatography (CH2Cl2/n-pentane, 1:2) furnished compound 17a (281 mg, 92%) as a colourless solid.

Workup

customwere then transferred via cannula at -20° C
extractionextracted with diethyl ether (3×50 mL)
dry with materialdried over anhydrous Na2SO4
filtrationAfter filtration
customthe solvent was evaporated in vacuo
customPurification by flash-chromatography (CH2Cl2/n-pentane, 1:2)

Sources & evidence

ORD record: ord-f368a4a194134be7940d651e233b15da
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334237B2

Reaction notes

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