2,6-Difluorophenol → HCID 58932509, compound

HRID 853762Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[OH:9].Cl[C:11]1[N:16]=[C:15]([NH:17][CH2:18][CH3:19])[C:14]([N+:20]([O-:22])=[O:21])=[CH:13][N:12]=1>C(N(CC)C(C)C)(C)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[O:9][C:11]1[N:16]=[C:15]([NH:17][CH2:18][CH3:19])[C:14]([N+:20]([O-:22])=[O:21])=[CH:13][N:12]=1

Participants

Conditions

Temperature: 130 °C

Procedure

2,6-Difluorophenol (2.1 g, 16.1 mmol) is added to a solution of (2-chloro-5-nitro-pyrimidin-4-yl)-ethyl-amine, 6, (3.0 g, 14.9 mmol) in N,N-diisopropyl ethylamine (50 mL). The reaction is heated to reflux (˜130° C.) under N2 for 3 hours at which point monitoring of the reaction via LC/MS indicates the starting material is consumed. The mixture is diluted with 1 N HCl (500 mL) and the resulting mixture extracted three times with EtOAc (500 mL). The organic layers are combined, dried over MgSO4 and concentrated in vacuo to an oil which is purified over silica (15% EtOAc/hexane) to afford 3.2 g (73% yield) of the desired product as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 9.07 (s, 1H), 8.43 (br s, 1H), 7.13-7.23 (m, 1H), 6.98 (t, J=7.8 Hz, 2H), 3.44-3.53 (m, 2H), 1.22 (t, J=7.2 Hz, 3H); ESI/MS: 297 (M+H).

Workup

temperatureThe reaction is heated
customat which point monitoring of the reaction via LC/MS
customis consumed
additionThe mixture is diluted with 1 N HCl (500 mL)
extractionthe resulting mixture extracted three times with EtOAc (500 mL)
dry with materialdried over MgSO4
concentrationconcentrated in vacuo to an oil which
customis purified over silica (15% EtOAc/hexane)

Sources & evidence

ORD record: ord-359b5e1459d349b3ba3ecade29e229d7
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07256196B1

Reaction notes

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