2-Fluorophenol → Tert-butyl 4-(5-(2-fluorophenoxyl)pyrimidin-2-yl)piperazine-1-carboxylate

HRID 522656Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[OH:28].C(=O)([O-])[O-].[Cs+].[Cs+]>N1C=CC=CC=1.C(OCC)(=O)C.[Cu]>[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[O:28][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (684 mg, 2.0 mmol), 2-fluorophenol (1.1 g, 10.0 mmol), copper (650 mg, 10.0 mmol) and cesium carbonate (6.5 g, 20.0 mmol) in pyridine (15 mL) was heated at 120 0° C. in a sealed tube overnight. The reaction mixture was diluted with ethyl acetate (200 mL) and then filtered. The filtrate was concentrated, and the residue was purified by silica gel chromatography (petroleum ether:ethyl acetate 20:1) to give tert-butyl 4-(5-(2-fluorophenoxyl)pyrimidin-2-yl)piperazine-1-carboxylate (50 mg, 6%) as a yellow solid. MS (ES+) C19H23FN4O3 requires: 374, found: 397 [M+Na]+.

Workup

filtrationfiltered
concentrationThe filtrate was concentrated
customthe residue was purified by silica gel chromatography (petroleum ether:ethyl acetate 20:1)

Sources & evidence

ORD record: ord-f8c3de02037a49d7874e63e5ecee6d70
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334263B2

Reaction notes

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