Cesium carbonate → Tert-butyl (4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamate

HRID 626569Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:18])=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:19](=[O:26])([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[NH2:20].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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.[Fe+2].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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:18][C:10]1[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:20][C:19](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH:7]=2)=[CH:14][CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[N:11]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of Example A3 (1.2 g, 4.52 mmol), t-butyl carbamate (1.058 g, 9.03 mmol), Cs2CO3 (2.94 g, 9.03 mmol) and DPPF (0.351 g, 0.632 mmol) in dioxane (25 mL) was sparged with Ar, treated with Pd2(dba)3 (0.290 g, 0.316 mmol), sparged again with Ar and heated at 100° C. for 3 days. The mixture was cooled to RT, diluted with EtOAc, the solids removed via filtration through diatomaceous earth and the filtrate concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford tert-butyl (4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamate (456 mg, 29%). MS (ESI) m/z: 347.2 (M+H+).

Workup

customsparged again with Ar
temperatureThe mixture was cooled to RT
additiondiluted with EtOAc
customthe solids removed via filtration through diatomaceous earth
concentrationthe filtrate concentrated to dryness
custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record: ord-383f2caff4064bbbb9f6c7fb2fb266c8
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309224B2

Reaction notes

Loading…