Potassium Carbonate → 2-nitro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)aniline

HRID 58211Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][CH2:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1.CCOC(C)=O.[Cl-].[Na+].O>CN(C=O)C>[N+:9]([C:3]1[CH:4]=[C:5]([O:8][CH2:19][CH2:20][O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH:6]=[CH:7][C:2]=1[NH2:1])([O-:11])=[O:10]

Participants

Conditions

Temperature: 50 °C

Procedure

4-amino-3-nitrophenol (2.0 g, 12.977 mmol) was dissolved in DMF (20 ml) and Potassium carbonate (3.59 g, 25.953 mmol) was added. To the mixture was added 2-(2-bromoethoxy)tetrahydro-2H-pyran (2.55 ml, 16.87 mmol) and the reaction mixture was stirred at 50° C. for 6 hours and then for 3 days at room temperature. The reaction mixture was poured into EtOAc/brine. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with brine three times, dried over MgSO4 and evaporated. The resulting material was purified by flash chromatography on silica eluting with 5% to 40% EtOAc/Hexane to afford title compound (1.4 g, yield: 38%). 1H-NMR (400 MHz, CDCl3) δ 1.51-1.68 (m, 4H) 1.71-1.89 (m, 2H) 3.46-3.61 (m, 1H) 3.72-3.99 (m, 2H) 4.03-4.24 (m, 3H) 4.64-4.79 (m, 1H) 6.78 (d, 1H) 7.09-7.17 (m, 1H) 7.60 (d, 1H).

Workup

waitfor 3 days at room temperature
extractionThe aqueous layer was extracted twice with EtOAc
washThe combined organic layer was washed with brine three times
dry with materialdried over MgSO4
customevaporated
customThe resulting material was purified by flash chromatography on silica eluting with 5% to 40% EtOAc/Hexane

Sources & evidence

ORD record: ord-df1948d4b5aa4ef19a3f1aa4ad508a49
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434697B2

Reaction notes

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