Urea → HCID 51347329, compound

HRID 924920Notes

Reaction equation

HRID 924920 reaction equation
[C:1]1([CH2:7][C:8]([C@H:10]2[CH2:14][CH2:13][CH2:12][O:11]2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH:21]=O)[CH3:16].[NH2:30][C:31]([NH2:33])=[O:32]>C(O)C.Cl>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:21]2[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:8]([C@H:10]3[CH2:14][CH2:13][CH2:12][O:11]3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH3:16]

Participants

6

Reactant 3

HCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 67060952HCID 67060952, compound2×

Product 1

HCID 51347329HCID 51347329, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Procedure

To a mixture of (R)-2-phenyl-1-(tetrahydrofuran-2-yl)ethanone (Intermediate 94) (200 mg, 1.0 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (266 mg, 1.3 mmol), and urea (189 mg, 3.2 mmol) in absolute ethanol (3 mL) was added conc. HCl (one drop). The mixture was refluxed under N2 for 3.5 hrs. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:2) and prep-HPLC (0.1% TFA as additive) to give Compound 176 (21 mg, yield 5%). 1H NMR (DMSO 400 MHz): δ 10.18 (s, 1H), 8.34 (s, 1H), 7.64 (s, 1H), 7.34-7.27 (m, 5H), 7.16-7.10 (m, 1H), 7.07-7.04 (m, 1H), 5.38 (s, 1H), 4.26-4.21 (m, 1H), 4.03-3.92 (m, 3H), 3.92-3.87 (m, 1H), 2.22-2.18 (m, 1H), 2.17-2.04 (m, 2H), 2.00-1.95 (m, 1H), 1.32-1.22 (m, 3H); MS (ESI): m/z 426.0[M+1]+.

Workup

  1. temperatureThe mixture was refluxed under N2 for 3.5 hrs
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompurified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:2) and prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-9e54195044fe44748e7c75fb54362969
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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