Triphosgene → Tert-butyl 3-((((2-nitro-5-(thiophen-2-yl)phenyl)carbamoyl)oxy)methyl)azetidine-1-carboxylate

HRID 2201680Notes

Reaction equation

HRID 2201680 reaction equation
[N+:1]([C:4]1[CH:10]=[CH:9][C:8]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].Cl[C:17](Cl)([O:19]C(=O)OC(Cl)(Cl)Cl)Cl.[OH:28][CH2:29][CH:30]1[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31]1>ClCCl>[N+:1]([C:4]1[CH:10]=[CH:9][C:8]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:7][C:5]=1[NH:6][C:17]([O:28][CH2:29][CH:30]1[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31]1)=[O:19])([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 10583745tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylateHCID 236564282-Nitro-5-(thiophen-2-yl)aniline

Product 1

HCID 70981903Tert-butyl 3-((((2-nitro-5-(thiophen-2-yl)phenyl)carbamoyl)oxy)methyl)azetidine-1-carboxylateYield 166%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 2-nitro-5-(thiophen-2-yl)aniline (0.30 g, 1.36 mmol, 1 eq.) and triphosgene (0.24 g, 0.82 mmol, 0.6 eq.) in dichloromethane (7 mL) at 0° C. was added TEA (0.38 mL, 2.90 mmol, 2 eq.). The reaction was stirred at room temperature for 2 h, then cooled down to 0° C. Tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (0.31 g, 1.64 mmol, 1.2 eq.) in dichloromethane (7 mL) and TEA (0.38 mL, 2.90 mmol, 2 eq.) were added at 0° C. The reaction was warmed to room temperature and stirred for 1 h. The reaction was diluted with dichloromethane and washed with citric acid solution then brine. The organic layer was separated, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography (silica gel, 25% EtOAc/hexanes) to obtain tert-butyl 3-((((2-nitro-5-(thiophen-2-yl)phenyl)carbamoyl)oxy)methyl)azetidine-1-carboxylate (0.59 g, 85% yield).

Workup

  1. temperaturecooled down to 0° C
  2. temperatureThe reaction was warmed to room temperature
  3. stirringstirred for 1 h
  4. washwashed with citric acid solution
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (silica gel, 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6ff5954347814cd08e2b6bfb8723395a
Source dataset
uspto-grants-2016_06
Patent number
US09365498B2

Reaction notes

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