Triphosgene → 1,1-Dimethylethyl 4-({[(2-bromo-6-fluoro-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

HRID 447782Notes

Reaction equation

HRID 447782 reaction equation
[Br:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4].Cl[C:12]([O:15]C(=O)OC(Cl)(Cl)Cl)(Cl)Cl.[NH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1>O1CCOCC1>[Br:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([F:10])[C:3]=1[NH:4][C:12]([NH:23][CH:24]1[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]1)=[O:15]

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 12682914-Amino-1-Boc-piperidineHCID 26598247Benzenamine, 2-bromo-6-fluoro-4-methyl-

Product 1

HCID 596832681,1-Dimethylethyl 4-({[(2-bromo-6-fluoro-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylateYield 129.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

2-Bromo-6-fluoro-4-methylaniline (5.2 g, 25.5 mmol) (D31) was dissolved in 1,4-dioxane (40 ml) and bis(trichloromethyl)carbonate (9.3 mmol, 2.7 g) was added at room temperature and the mixture was heated to 60° C. for 15 minutes and it was then brought up to 100° C. for a further 15 minutes. The mixture was then cooled to room temperature, filtered and the solvent was thoroughly evaporated; the crude was redissolved in dichloromethane (40 ml) and 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (2 eq., 51 mmol, ˜10.2 g) was added at room temperature very slowly. The mixture was stirred at room temperature for 1.5 hours, the solvent was then evaporated totally and the crude material was then left under vacuum for 10 minutes; dichloromethane was added again and the mixture obtained was filtered to afford the solid that is the first batch (5.2 g) of the desired product; the solvent was evaporated from the organic filtrate and the mixture obtained was re-dissolved into dichloromethane and filtered again to afford the second batch (1 g) of the desired product; the solvent was evaporated from the organic filtrate and the mixture obtained was re-dissolved into diethyl ether, filtered again, washed with methanol then with diethyl ether to afford the third batch (1.5 g) of the desired product. The three batches were combined to afford 7.7 g of the title compound, 70%, M++H=432.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. filtrationfiltered
  3. customthe solvent was thoroughly evaporated
  4. dissolutionthe crude was redissolved in dichloromethane (40 ml)
  5. customthe solvent was then evaporated totally
  6. waitthe crude material was then left under vacuum for 10 minutes
  7. additiondichloromethane was added again
  8. customthe mixture obtained
  9. filtrationwas filtered
  10. customto afford the solid

Sources & evidence

ORD record
ord-fd28ba3582b74bc586ec6b23b3738be6
Source dataset
uspto-grants-2013_07
Patent number
US08481566B2

Reaction notes

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