Urea → HCID 51347190, compound

HRID 924919Notes

Reaction equation

HRID 924919 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 67060956HCID 67060956, compound2×

Product 1

HCID 51347190HCID 51347190, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Procedure

To a mixture of (S)-2-phenyl-1-(tetrahydrofuran-2-yl)ethanone (Intermediate 93) (150 mg, 0.8 mmol), 3-ethoxy-4-hydroxy-5-nitro-benzaldehyde (200 mg, 0.9 mmol), and urea (142 mg, 2.4 mmol) in absolute ethanol (3 mL) was added conc. HCl (one drop). The mixture was refluxed under N2 for 3 hrs. The reaction mixture was concentrated in vacuo, and was 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 175 (30 mg, yield 9%). 1H NMR (DMSO 400 MHz): δ 10.28-10.16 (m, 1H), 7.65-7.45 (m, 0.5H), 7.40-7.17 (m, 4.5H), 7.10-7.03 (m, 1.5H), 6.98-6.95 (m, 0.5H), 5.38-5.36 (s, 0.5H), 5.16-5.08 (m, 0.5H), 4.30-4.20 (m, 0.5H), 4.10-3.85 (m, 3H), 3.62-3.53 (m, 0.5H), 2.21-1.65 (m, 3.5H), 1.31-1.19 (m, 3H); MS (ESI): m/z 426.1 [M+1]+.

Workup

  1. temperatureThe mixture was refluxed under N2 for 3 hrs
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customwas purified 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-8725cc4076e64f03b8abc6fab94735f4
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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