Urea → HCID 51347331, compound

HRID 401132Notes

Reaction equation

HRID 401132 reaction equation
[NH2:1][C:2]([NH2:4])=[O:3].[CH2:5]([O:7][C:8]1[CH:9]=[C:10]([CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[C:15]=1[OH:16])[CH:11]=O)[CH3:6].B(F)(F)F.CCOCC.[CH:29]1([CH2:35][C:36]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=O)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>C1COCC1.Cl[Cu].CC(O)=O>[CH:38]1([C:36]2[CH:11]([C:10]3[CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[C:15]([OH:16])=[C:8]([O:7][CH2:5][CH3:6])[CH:9]=3)[NH:1][C:2](=[O:3])[NH:4][C:35]=2[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1

Participants

8

Reactant 4

HCID 1176UreaHCID 8000Boron trifluoride etherateHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 10921586HCID 10921586, compound2×

Product 1

HCID 51347331HCID 51347331, compoundYield 9.3%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of urea (150 mg, 2.5 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (104 mg, 0.49 mmol), CuCl (99 mg, 1.0 mmol), BF3-Et2O (142 mg, 1.0 mmol) and AcOH (0.2 mL) in anhydrous THF (10 mL) was stirred under refluxing under N2 atmosphere for 0.5 hour. Then 2-cyclohexyl-1-phenylethanone (Intermediate 96) (100 mg, 0.49 mmol) in anhydrous THF (0.5 mL) was added and the reaction mixture was refluxed overnight. Followed a standard aqueous/EtOAc workup and purified by prep-HPLC (0.1% TFA as additive) to give Compound 177 (20 mg, yield 9%). 1H NMR (CD3OD 400 MHz): δ 7.74 (d, J=2.0 Hz, 1H), 7.53-7.38 (m, 6H), 7.39 (d, J=2.0 Hz, 1H), 4.99 (s, 1H), 4.21 (q, J=7.2 Hz, 1H), 2.35-2.28 (m, 1H), 1.69 (m, 1H), 1.64 (m, 1H), 1.55-1.47 (m, 7H), 1.05-0.92 (m, 3H), 0.85-0.79 (m, 1H). MS (ESI): m/z 438.3 [M+1]+.

Workup

  1. temperatureunder refluxing under N2 atmosphere for 0.5 hour
  2. temperaturethe reaction mixture was refluxed overnight
  3. customFollowed a standard aqueous/EtOAc workup and purified by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-ee13e560e6b646ddbcae5f8c47731d9f
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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