Triphosgene → HCID 22490380, compound

HRID 2180184Notes

Reaction equation

HRID 2180184 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][CH2:11][NH:12][CH2:13][C:14]2([C:21]3[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=3)[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:5]=[CH:6][C:7]=1[F:8].Cl[C:29](Cl)([O:31]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:10][CH2:11][N:12]([CH2:13][C:14]3([C:21]4[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=4)[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH2:19]3)[C:29]2=[O:31])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 2

HCID 94429TriphosgeneHCID 68535370HCID 68535370, compound

Product 1

HCID 22490380HCID 22490380, compoundYield 6.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of N-(3,4-difluoro-phenyl)-N′-[4-(4-iodo-phenyl)-1-methyl-piperidin-4-ylmethyl]-ethane-1,2-diamine (0.36 g, 1.0 mmol) in THF (10 mL) at 0° C. was added TEA (0.91 mL, 6.5 mmol, 6.5 eq.) and triphosgene (0.195 g, 0.65 mmol, 0.65 eq.). The mixture was stirred at room temperature for 4 h, diluted with EtOAc (25 mL) and washed with saturated brine (2×25 mL). The organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation to give a yellow oil. The crude product was purified by flash column chromatography by eluting with 2% MeOH/CH2Cl2 to give 1-(3,4-difluoro-phenyl)-3-[4-(4-iodo-phenyl)-1-methyl-piperidin-4-ylmethyl]-imidazolid in-2-one (0.023 g, 0.045 mmol, 5%) as a pale foam. MS (ESI): 512.1/513.1 (M+H), impurity peak 690.9/692.0.

Workup

  1. washwashed with saturated brine (2×25 mL)
  2. dry with materialThe organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated by rotary evaporation
  5. customto give a yellow oil
  6. customThe crude product was purified by flash column chromatography
  7. washby eluting with 2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-da097b18cfc94c67ac030673889d20b0
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

Loading…