Sodium Carbonate → 2-Chloro-4-(5-fluoro-4-formylpyridin-3-yl)benzonitrile

HRID 1897586Notes

Reaction equation

[Cl:1][C:2]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[C:20]1[CH:27]=[N:26][CH:25]=[C:24]([F:28])[C:21]=1[CH:22]=[O:23].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:9]=[C:8]([C:20]2[CH:27]=[N:26][CH:25]=[C:24]([F:28])[C:21]=2[CH:22]=[O:23])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

Conditions

Temperature: 100 °C

Procedure

To the solution of 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (264 mg, 1.00 mmol), 3-bromo-5-fluoroisonicotinaldehyde (204 mg, 1.00 mmol) and PdCl2(PPh3)2 (56 mg, 0.08 mmol) in DMF (3 mL) was added 2M Na2CO3 solution (1.50 ml, 3.00 mmol) under nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 4 hrs. After letting cool to room temperature, solvent was removed in vacuo. The resulting residue was dissolved in DCM and saturated NH4Cl solution. After extraction and separation, the combined extracts were concentrated and purified by SNAP10 g (10% MeOH/DCM 0-15% gradient) to give 2-chloro-4-(5-fluoro-4-formylpyridin-3-yl)benzonitrile (47 mg, 18%) as a white solid; ESI-MS m/z: 293 [M+MeOH+1]+, Retention time 1.15 min. 1H-NMR (CDCl3, 400 MHz) δ 7.33 (dd, J=8.0, 1.6 Hz, 1H), 7.50 (d, J=1.6 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 8.49 (s, 1H), 8.78 (d, J=1.2 Hz, 1H), 10.27 (s, 1H).

Workup

temperatureAfter letting cool to room temperature
customsolvent was removed in vacuo
dissolutionThe resulting residue was dissolved in DCM
extractionAfter extraction and separation
concentrationthe combined extracts were concentrated
custompurified by SNAP10 g (10% MeOH/DCM 0-15% gradient)

Sources & evidence

ORD record: ord-5060bd4428a94798a8e2c37274ca53e6
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08519134B2

Reaction notes

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