Triethylamine → HCID 118114911, compound

HRID 1050586Notes

Reaction equation

HRID 1050586 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][CH2:9][CH2:10][NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:9][CH2:10][N:11]([C@@H:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[C:33]2=[O:35])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 118115224HCID 118115224, compound

Product 1

HCID 118114911HCID 118114911, compoundYield 106%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In ice bath and under N2 atmosphere, to a stirred solution of (R)-tert-butyl 3-(2-(3-chlorophenylamino)ethylamino)piperidine-1-carboxylate (398) (10.1 g, 28.37 mmol) and Et3N (3.01 g, 29.8 mmol) in anhydrous DCM (300 mL) was added a solution of triphosgene (2.95 g, 9.93 mmol) in DCM (100 mL) dropwise. The resulting mixture was stirred in ice bath for 1 hour, and quenched with NaHCO3 (aq.) (1M, 50 mL). The mixture was extracted with DCM (100 mL×3). The combined organic layer was washed with brine, dried, concentrated and subjected to silica flash column chromatography using 0 to 5% MeOH in DCM to isolate (R)-tert-butyl 3-(3-(3-chlorophenyl)-2-oxoimidazolidin-1-yl)piperidine-1-carboxylate (399) (4 g, 37%) as a white solid. It was treated with 40 mL commercial 4N HCl in dioxane to give (R)-1-(3-chlorophenyl)-3-(piperidin-3-yl)imidazolidin-2-one hydrochloride (400) (3.3 g, quant.) as a white solid. Proton NMR (DMSO-d6): δ 9.26 (1H, s), 8.93 (1H, s), 7.77 (1H, t, J=2.0 Hz), 7.47-7.40 (1H, m), 7.35 (1H, t, J=8.1 Hz), 7.06 (1H, dd, J=7.9, 1.1 Hz), 4.10-3.94 (1H, m), 3.89-3.76 (2H, m), 3.48 (2H, t, J=8.5 Hz), 3.25-3.14 (2H, m), 3.06-2.97 (1H, m), 2.82-2.72 (1H, m), 1.95-1.86 (1H, m), 1.83-1.68 (3H, m) ppm.

Workup

  1. customquenched with NaHCO3 (aq.) (1M, 50 mL)
  2. extractionThe mixture was extracted with DCM (100 mL×3)
  3. washThe combined organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-dfcedb503f2945bc9b84d2d6f1bcef90
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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