Triethylamine → 2-fluorophenyl N-[7-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)heptan-2-yl]carbamate

HRID 412209Notes

Reaction equation

HRID 412209 reaction equation
C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:8])C=CC=CC=1.[CH3:18][CH:19]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][N:28]1[C:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:30]=[C:29]1[CH3:45])C(O)=O.C([N:48]([CH2:51]C)CC)C.[F:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[OH:60]>C1(C)C=CC=CC=1.O.ClCCl.C(OCC)(=O)C>[F:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[O:60][C:51](=[O:8])[NH:48][CH:19]([CH3:18])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][N:28]1[C:32]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:30]=[C:29]1[CH3:45]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 97072-FluorophenolHCID 199401P,P-Diphenylphosphinic azideHCID 185375322-Methyl-7-(2-methyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid

Product 1

HCID 101170002-fluorophenyl N-[7-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)heptan-2-yl]carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

(Scheme 3 (Q)) Diphenylphosphoryl Azide (0.083 ml, 0.38 mmole) was added to a suspension of starting material 2-methyl-7-(2-methyl-4,5-diphenyl-imidazol-1-yl)-heptanoic acid (120 mg, 0.32 mmole) and Triethylamine (0.14 ml, 1.005 mmole) in Toluene (5 ml) at room temperature. The reaction mixture was let stirred at room temperature for 10 minutes under Nitrogen, then at 108° C. for 90 minutes. The reaction was let cooled to room temperature, to which 2-Fluorophenol (0.03 ml, 0.038 g, 0.338 mmole) was added. The reaction mixture was let stirred at room temperature for 30 minutes, then at 100° C. for 18 hrs. The next day, analysis by TLC (Dichloromethane/Ethyl Acetate 3:1) indicated consumption of starting material. The reaction was let cooled to room temperature, where the solvent was removed by rotorvap. The crude material was purified by flash column chromatography using Dichloromethane/Ethyl Acetate (6:1 to 3:1). Product was obtained (110 mg, 71%). 1H NMR (CDCl3): δ1.21 (d, J=8.75 mHz, 6H), 1.35 (m, 2H), 1.51 (m, 2H), 2.50 (s, 3H), 3.71 (m, 3H), 4.93 (b, 1H), 7.18 (m, 6H), 7.32 (m, 2H), 7.46 (m, 6H). 13C NMR (CDCl3): 813.7, 21.1, 25. 2, 30.3, 36.7, 43.7, 47.5, 116.5, 116.650, 124.132, 124.325, 125.943, 126.520, 128.027, 128.347, 128.509, 129.018, 131.101, 131.796, 134.8,136.4, 138.6, 144.1,153.0, 153.7, 155.6. Anal. Calcd. for C30H32FN3O2.0.42 H2O: C, 73.06; H, 6.71; N, 8.52. Found: C, 73.24; H, 6.82; N, 8.29. Mass Spec: 486.27 (MH+).

Workup

  1. waitat 108° C. for 90 minutes
  2. additionwas added
  3. stirringThe reaction mixture was let stirred at room temperature for 30 minutes
  4. waitat 100° C. for 18 hrs
  5. customconsumption of starting material
  6. temperatureThe reaction was let cooled to room temperature
  7. customwhere the solvent was removed by rotorvap
  8. customThe crude material was purified by flash column chromatography
  9. customProduct was obtained (110 mg, 71%)

Sources & evidence

ORD record
ord-17e1b3da45584cd5bd62d2465231c525
Source dataset
uspto-grants-2003_05
Patent number
US06562846B2

Reaction notes

Loading…