4-Fluorophenol → 6-(4-Fluorophenoxy)phthalazin-1-ol

HRID 2357540Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[N:7][N:6]=[CH:5]2.[F:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>ClCCl.[Cu]Cl.CN1CCCC1=O>[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8]([OH:12])=[N:7][N:6]=[CH:5]3)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A 100-mL round-bottom flask under argon was charged with 6-bromophthalazin-1-ol (0.5 g, 2 mmol), 4-fluorophenol (0.4 mL, 4 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.04 mL, 0.2 mmol), cesium carbonate (1 g, 4 mmol), and 1-methyl-2-pyrrolidinone (4 mL), followed by copper (I) chloride (0.1 g, 1 mmol). The reaction mixture was heated at 120° C. for 20 h. The reaction mixture was cooled, diluted with dichloromethane, and washed with water. The pH of the aqueous layer was adjusted to ˜7 with saturated aqueous NaHCO3 and extracted with DCM (2×). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. Flash chromatography eluting with 1%, 2%, 3%, and 5% MeOH/CHCl3 gave the title compound. MS (ES+): 257.1 (M+H)+.

Workup

temperatureThe reaction mixture was cooled
washwashed with water
extractionextracted with DCM (2×)
dry with materialThe combined organic extracts were dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
washFlash chromatography eluting with 1%, 2%, 3%, and 5% MeOH/CHCl3

Sources & evidence

ORD record: ord-9eac223aa12f4056940a09962ca7224f
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07759337B2

Reaction notes

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