Sodium Carbonate → 5-Nitro-2-(2,2,6,6-tetramethyl-3,6-dihydro-2H-pyran-4-yl)-pyridine

HRID 456003

Reaction equation

[CH3:1][C:2]1([CH3:19])[CH2:7][C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][C:4]([CH3:18])([CH3:17])[O:3]1.C([O-])([O-])=O.[Na+].[Na+].[Li+].[Cl-].Br[C:29]1[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][N:30]=1>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+:35]([C:32]1[CH:33]=[CH:34][C:29]([C:6]2[CH2:7][C:2]([CH3:1])([CH3:19])[O:3][C:4]([CH3:17])([CH3:18])[CH:5]=2)=[N:30][CH:31]=1)([O-:37])=[O:36]

Participants

Conditions

Temperature: 80 °C

Procedure

2,2,6,6-Tetramethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (as prepared in the previous step) (18.5 g, 0.069 mol) was dissolved in dimethoxyethane (DME) (350 mL). The resulting solution was treated with 2 M Na2CO3 (280 mL, 0.560 mol), LiCl (5.00 g, 0.110 mol) and 2-bromo-5-nitropyridine (14.0 g, 0.060 mol). The resulting mixture was degassed by sonication for 30 min under Ar and then Pd(PPh3)4 (8.00 g, 6.90 mmol) was added and the reaction heated at 80° C. under Ar overnight. The reaction mixture was allowed to cool to RT and extracted with EtOAc (3×150 mL). The residue was purified on silica gel with 2-10% EtOAc:hexane to obtain the title compound as a pale yellow solid (15.2 g, 83%). 1H-NMR (CDCl3; 400 MHz): δ 9.40 (d, 1H, J=2.8 Hz), 8.45 (dd, 1H, J=8.8, 2.8 Hz), 7.59 (d, 1H, J=8.8 Hz), 6.90 (t, 1H, J=1.6 Hz), 2.5 (d, 1H, J=1.6 Hz), 1.40 (s, 6H), 1.34 (s, 6H).

Workup

customThe resulting mixture was degassed by sonication for 30 min under Ar
temperatureto cool to RT
extractionextracted with EtOAc (3×150 mL)
customThe residue was purified on silica gel with 2-10% EtOAc

Sources & evidence

ORD record: ord-dd9cf3a83da04bdfa445c75036224dbb
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497376B2

Linked notes

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