Imidazole → Tert-butyl 4-(2-(2-iodoethylthio)-5-nitrophenylamino)piperidine-1-carboxylate

HRID 424580Notes

Reaction equation

HRID 424580 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:25]I.O[CH2:28][CH2:29][S:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][C:32]=1[NH:40][CH:41]1[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][CH2:42]1>O1CCCC1.C(OCC)(=O)C>[I:25][CH2:28][CH2:29][S:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][C:32]=1[NH:40][CH:41]1[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][CH2:42]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 59144148HCID 59144148, compound

Product 1

HCID 59144149Tert-butyl 4-(2-(2-iodoethylthio)-5-nitrophenylamino)piperidine-1-carboxylateYield 99%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of triphenylphosphine (1.178 g, 4.49 mmol) and imidazole (0.611 g, 8.98 mmol) in tetrahydrofuran (10 mL) at 0° C. was added iodine (1.292 g, 5.09 mmol). The resulting dark mixture was stirred at 0° C. After 5 minutes, tert-butyl 4-(2-(2-hydroxyethylthio)-5-nitrophenylamino)piperidine-1-carboxylate (1.19 g, 2.99 mmol) was added as a solution in tetrahydrofuran (5 mL). The mixture was then warmed to room temperature and stirred for 1 hour. The mixture was then diluted with ethyl acetate and washed with saturated sodium carbonate, saturated sodium thiosulfate, water, and brine. The organic phase was dried, filtered, concentrated, and then chromatographed in 1:2 ethyl acetate:hexanes, giving the desired product (1.50 g, 99%) as an orange foam. 1H NMR (DMSO-d6) δ 7.59-7.54 (m, 1H), 7.45-7.38 (m, 2H), 5.45-5.37 (m, 1H), 3.98-3.85 (m, 2H), 3.73-3.61 (m, 1H), 3.35-3.27 (m, 5H), 3.19-3.03 (m, 1H), 3.02-2.82 (m, 2H), 1.92-1.84 (m, 2H), 1.45-1.34 (m, 11H); ESI-MS (m/z, %): 530 (M+Na, 6), 452 (25), 279 (100).

Workup

  1. temperatureThe mixture was then warmed to room temperature
  2. stirringstirred for 1 hour
  3. washwashed with saturated sodium carbonate, saturated sodium thiosulfate, water, and brine
  4. customThe organic phase was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed in 1:2 ethyl acetate

Sources & evidence

ORD record
ord-78abd6a4a7ea430f8441e870c87bfdac
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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