Phenol → HCID 178513671, compound

HRID 130888Notes

Reaction equation

[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=1.[C:18]([O-:21])([O-])=O.[K+].[K+].C[N:25]([CH:27]=O)C.[C:29]1([CH3:35])[CH:34]=[CH:33]C=[CH:31][CH:30]=1>>[OH:7][C@H:1]1[CH2:6][CH2:5][C@H:4]([NH:25][CH2:27][CH2:35][C:29]2[CH:34]=[CH:33][C:18]([O:21][C:9]3[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=3)=[CH:31][CH:30]=2)[CH2:3][CH2:2]1

Participants

Reactant 4

HCID 996Phenol

HCID 11430Potassium Carbonate

HCID 804566-Chloronicotinamide

HCID 21735183Dimethylformamide toluene

Product 1

HCID 178513671HCID 178513671, compoundYield 43%

Procedure

Heat a mixture of the phenol (121.2 mg, 0.52 mmol), 6-chloronicotinamide (121.0 mg, 0.77 mmol), and K2CO3 (213.5 mg, 1.55 mmol) in 3:1 DMF/toluene (6.0 mL) at 165° C. for 3 hours. Quench the reaction with a small amount of H2O and concentrate to dryness, using xylenes to remove DMF azeotropically. Dissolve the residue in MeOH and filter. Concentrate the filtrate and purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH, to afford the title compound (79.1 mg, 43%): MS ES+ 356.0 (M+H)+, HRMS calcd for C20H26N3O3 356.1974 (M+H)+, found 356.1959, time 0.34 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 5-95% over 19 min], tR=5.81 min, 100% purity.

Workup

temperatureHeat
customQuench
customthe reaction with a small amount of H2O
concentrationconcentrate to dryness
customto remove DMF azeotropically
dissolutionDissolve the residue in MeOH
filtrationfilter
concentrationConcentrate the filtrate
custompurify by flash chromatography
washeluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH

Sources & evidence

ORD record: ord-102ef556848749aaafc92341839a1ee7
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07381719B2

Reaction notes

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