Tetrahydrofuran → 5-Cyclohex-1-enyl-6-(2,2,2-trifluoroethoxy)nicotinic acid methylester

HRID 469768

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[C:9](Br)[CH:10]=1)=[O:4].[C:18]1(B2OC(C)(C)C(C)(C)O2)[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:1][O:2][C:3](=[O:4])[C:5]1[CH:10]=[C:9]([C:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=2)[C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:7][CH:6]=1

Participants

Conditions

Temperature: 70 °C

Procedure

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid methyl ester (CAN 1211589-51-3), 200 mg, 637 μmol), 2-cyclohexenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAN 141091-37-4, 119 mg, 123 μA, 574 μmol), K3PO4 (409 mg, 1.91 mmol) and PdCl2(dppf)-CH2Cl2 adduct (26.0 mg, 31.8 μmol) were combined in degassed DMF (4.38 mL)/THF (1.46 mL) to give a yellow suspension. The mixture was heated to 70° C. and shaken overnight. After cooling the mixture was poured into 100 mL saturated NaHCO3/ice water and extracted with i-propyl acetate (2×100 mL). The organic layers were washed with ice/brine (1×150 mL), combined, dried with Na2SO4 and concentrated in vacuo to give 283 mg of a brown oil. The crude material was purified by preparative TLC (silica gel, 2×2.0 mm, n-heptane/iPrOAc 9:1) to give the title compound (129 mg, 64%) as colorless solid; MS (ESI) 316.2 (M+H)+.

Workup

customto give a yellow suspension
temperatureAfter cooling the mixture
extractionextracted with i-propyl acetate (2×100 mL)
washThe organic layers were washed with ice/brine (1×150 mL)
dry with materialdried with Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-844f17dc9dc94df3a098a9f7cccde8c1
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629166B2

Linked notes

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