4-Fluorobenzylamine → tert-butyl (4S,5R)-2-[(4-fluorophenyl)methylamino]-4,5-diphenyl-4,5-dihydroimidazole-1-carboxylate

HRID 2053526

Reaction equation

HRID 2053526 reaction equation
[C:1]1([C@H:7]2[C@@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:9](SC)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1>CO>[C:21]([O:20][C:18]([N:10]1[C@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=[C:9]1[NH:33][CH2:32][C:31]1[CH:34]=[CH:35][C:28]([F:27])=[CH:29][CH:30]=1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

4

Reactant 2

HCID 673264-FluorobenzylamineHCID 86596320cis-4,5-Diphenyl-2-methylthio-4,5-dihydro-imidazole-1-carboxylic Acid, Tert-Butyl Ester

Product 1

HCID 68568680tert-butyl (4S,5R)-2-[(4-fluorophenyl)methylamino]-4,5-diphenyl-4,5-dihydroimidazole-1-carboxylateYield 41.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of intermediate 59 (1.0 g, 0.0027 mol), 4-fluorobenzylamine (0.372 mL, 0.00321 mol) and MeOH (0.4 mL) is heated at 100° C. for 2 days. The reaction mixture is cooled to RT, and partitioned between dichloromethane and water. The organic solution is separated, dried (MgSO4), and concentrated in vacuo. The residue is purified by chromatography on silica gel; gradient elution with heptane:EtOAc (80:20-40:60) gives 0.50 g of the product 85. 1H NMR (CDCl3) δ 7.60-7.35 (m, 3H), 7.15-6.90 (m, 10H), 6.85-6.70 (m, 2H), 5.50-5.30 (m, 2H), 5.75-5.55 (m, 2H), 1.12 (s, 9H); MS: m/z 446 (M++1).

Workup

  1. temperatureThe reaction mixture is cooled to RT
  2. custompartitioned between dichloromethane and water
  3. customThe organic solution is separated
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by chromatography on silica gel
  7. washgradient elution with heptane:EtOAc (80:20-40:60)

Sources & evidence

ORD record
ord-c8791c0e2c9448708eaf47ed6d2181c5
Source dataset
uspto-grants-2008_02
Patent number
US07326792B2

Linked notes

Loading…