Chlorosuccinimide → HCID 178454146, compound

HRID 1176096Notes

Reaction equation

HRID 1176096 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]([C:16]1[NH:17][C:18]([Cl:22])=[C:19](Br)[N:20]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N(Cl)C(=O)C1>C(#N)C>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]([C:16]1[NH:20][CH:19]=[C:18]([Cl:22])[N:17]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 57976384HCID 57976384, compound

Product 1

HCID 178454146HCID 178454146, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

[(S)-1-(4-Bromo-5-chloro-1H-imidazol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester: To a suspension of 141C (5.0 g, 17 mmol) in acetonitrile (400 mL) at 0° C. was added NCS (2.3 g, 17 mmol). The reaction mixture was stirred at 0° C. for 1 h, then at rt for 1 h followed by 50° C. overnight. The reaction mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water and brine, dried over sodium sulfate, and concentrated. The crude was purified by flash column chromatography to give [(S)-1-(4-chloro-1H-imidazol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester as white solid (2 g, 36%). LCMS m/z 321 (M+H)+. To a solution of this intermediate (2 g, 6.20 mmol) in chloroform was added NBS (1.2 g, 6.8 mmol) and the reaction mixture was stirred at rt for 20 min. The reaction was quenched with water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The crude product was purified by crystallization from hexane to give 141D as an off-white solid (1.7 g, 71%). LC/MS m/z 400 (M+H)+. 1HNMR (CDCl3, 400 MHz) δ 7.28 (m, 3H), 7.12 (d, 2H), 5.33 (d, 1H), 4.81 (d, 1H), 3.27 (dd, 2H), 1.3 (s, 9H).

Workup

  1. waitat rt for 1 h followed by 50° C. overnight
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude was purified by flash column chromatography

Sources & evidence

ORD record
ord-6b2c73d621b1496f802c910a9541ecbb
Source dataset
uspto-grants-2010_11
Patent number
US07842708B2

Reaction notes

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