1,1-Dichloroethane → tert-butyl 4-(4,5-dichloro-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088879Notes

Reaction equation

HRID 2088879 reaction equation
[NH:1]1C=C[N:3]=[C:2]1[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.[Cl:19]N1C(=O)CCC1=O.Cl[CH:28]([Cl:30])[CH3:29]>>[Cl:19][C:29]1[N:1]=[C:2]([CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[NH:3][C:28]=1[Cl:30]

Participants

4

Reactant 3

HCID 63651,1-DichloroethaneHCID 31398ChlorosuccinimideHCID 17840015tert-butyl 4-(1H-imidazol-2-yl)piperidine-1-carboxylate

Product 1

HCID 67112013tert-butyl 4-(4,5-dichloro-1H-imidazol-2-yl)piperidine-1-carboxylateYield 29%

Procedure

Add tert-butyl 4-(1H-imidazol-2-yl)piperidine-1-carboxylate (6.00 g, 23.87 mmol) in dichloroethane (200 mL). Add N-chlorosuccinimide (3.19 g, 1.0 eq). Stir at room temperature under nitrogen for 14 hours. Concentrate the reaction mixture in vacuo. Purify by silica gel chromatography, eluting with hexanes to 9:1 hexanes:ethyl acetate to 4:1 hexanes:ethyl acetate to 2:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate, to give two major spots. Concentrate fractions containing the higher Rf spot in vacuo to give tert-butyl 4-(4,5-dichloro-1H-imidazol-2-yl)piperidine-1-carboxylate (2.25 g, 29%). MS (ES) m/z=321 [M]+. Concentrate fractions containing the lower spot in vacuo. Slurry the resulting solid into diethyl ether/chloroform, then filter. Concentrate the filtrate in vacuo to give tert-butyl 4-(4-chloro-1H-imidazol-2-yl)piperidine-1-carboxylate (1.16 g, 17%). MS (ES) m/z=286 [M]+.

Workup

  1. concentrationConcentrate the reaction mixture in vacuo
  2. customPurify by silica gel chromatography
  3. washeluting with hexanes to 9:1 hexanes
  4. customethyl acetate to 4:1 hexanes:ethyl acetate to 2:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate, to give two major spots
  5. additionConcentrate fractions containing the higher Rf spot in vacuo

Sources & evidence

ORD record
ord-efbb5d5ee9bf4422ba3b86fb4c050ad9
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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