Potassium Phosphate, Tribasic → 4-Amino-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridine-2-carbonitrile

HRID 1481593Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[N+:11]([O-:13])=[O:12].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O>O1CCOCC1.CCOC(C)=O.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[CH:7]=[C:6]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[C:23]([F:34])([F:33])[F:22])[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[N+:11]([O-:13])=[O:12]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 4-amino-6-chloro-3-nitro-pyridine-2-carbonitrile (186 mg, 0.937 mmol) in 1,4-dioxane (5 mL) was treated with K3PO4 (1.00 g, 5.10 mmol), 2-trifluoromethylphenylboronic acid (178 mg, 0.937 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene (60.5 mg, 0.128 mmol) and Pd(OAc)2 (28.6 mg, 0.128 mmol). The resulting mixture was stirred 80° C. overnight. The cooled mixture was diluted with EtOAc (50 mL) and washed with water (50 mL). The aqueous layer was extracted twice with EtOAc (30 mL) and the combined extracts were dried over MgSO4 and concentrated in vacuo. The resulting residue was purified on silica (0:100-100:0 EtOAc-hexanes) to yield 4-amino-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridine-2-carbonitrile. 1H-NMR (400 MHz, CDCl3) δ: 7.79 (m, 1H), 7.67 (m, 4H), 7.52 (m, 1H), 7.04 (s, 1H).

Workup

washwashed with water (50 mL)
extractionThe aqueous layer was extracted twice with EtOAc (30 mL)
dry with materialthe combined extracts were dried over MgSO4
concentrationconcentrated in vacuo
customThe resulting residue was purified on silica (0:100-100:0 EtOAc-hexanes)

Sources & evidence

ORD record: ord-e306171e1f9f49a180703ac30d95b366
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409915B2

Reaction notes

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