1,1-Dichloroethane → 1-((1R,2R)-2-(benzyloxy)cyclohexyl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylic acid

HRID 1685113

Reaction equation

HRID 1685113 reaction equation
[CH2:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]([NH2:18])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:19](=[C:21]([C:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[N-].ClC(Cl)C.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCC(O)=O.[Rh].[Rh]>[CH2:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[N:15]1[C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:21]([C:22]([OH:24])=[O:23])[NH:18][C:16]1=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[N:15]1[C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[NH:19][C:16]1=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 63651,1-DichloroethaneHCID 6422Trifluoroacetic acidHCID 605325Acetic acid, benzoyldiazo-, ethyl ester2×HCID 592922781-((1R,2R)-2-(benzyloxy)cyclohexyl)urea

Product 2

HCID 592923041-((1R,2R)-2-(benzyloxy)cyclohexyl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylic acidHCID 59292756ethyl 1-((1R,2R)-2-(benzyloxy)cyclohexyl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6099591Rhodium(II) Octanoate DimerCatalystHCID 1140TolueneSolvent2×

Procedure

A flask containing a mixture of 15B (3.20 g, 12.87 mmol), ethyl 2-diazo-3-oxo-3-phenylpropanoate (15C) (2.25 g, 10.31 mmol), and 103 mL of 1:1 toluene:dichloroethane was heated at 80° C. for about 10 minutes. A suspension of rhodium octanoate dimer (0.16 g, 0.21 mmol) in 25 mL toluene was added dropwise to the reaction mixture via addition funnel. The reaction was held at 80° C. for an additional hour after addition was completed. After the disappearance of 15C, the reaction was cooled to RT. Approximately 8 mL of TFA was then added and the reaction was allowed to stir overnight at RT. The reaction mixture was concentrated to a green oil then purified by flash chromatography on silica gel using 5-40% ethyl acetate/hexanes to afford the desired product ethyl 1-((1R,2R)-2-(benzyloxy)cyclohexyl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylate as a tan solid (15D) (2.20 g, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96 (t, J=7.07 Hz, 4H) 1.16 (d, J=12.13 Hz, 1H) 1.56-1.67 (m, 2H) 1.72 (d, J=12.13 Hz, 1H) 2.11 (d, J=6.82 Hz, 1H) 2.32 (d, J=8.84 Hz, 1H) 3.25 (br. s., 1H) 3.98 (q, J=7.07 Hz, 2H) 4.19-4.31 (m, 3H) 4.51 (d, J=11.87 Hz, 1H) 7.15 (d, J=7.33 Hz, 2H) 7.23-7.34 (m, 1H) 7.28 (dd, J=7.71, 1.64 Hz, 4H) 7.43 (br. s., 3H) 10.86 (s, 1H). ESI-MS: m/z 421.4 (M+H)+.

Workup

  1. additionA flask containing
  2. additionwas added dropwise to the reaction mixture via addition funnel
  3. waitThe reaction was held at 80° C. for an additional hour
  4. additionafter addition
  5. concentrationThe reaction mixture was concentrated to a green oil
  6. customthen purified by flash chromatography on silica gel using 5-40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8b39ff2950c642788122fb130d2e74a2
Source dataset
uspto-grants-2012_04
Patent number
US08148367B2

Linked notes

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