Phosgene → [2'-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid methyl ester

HRID 1810281Notes

Reaction equation

HRID 1810281 reaction equation
[CH3:1][O:2][C:3](=[O:27])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH2:23][NH:24][CH2:25][CH3:26])[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.C(N(C(C)C)CC)(C)C.[C:37](Cl)(Cl)=[O:38].[CH2:41]([NH2:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:27])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][C:14]=2[CH2:23][N:24]([CH2:25][CH3:26])[C:37]([NH:48][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:38])[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 7504Benzylamine2×HCID 8471TriethylamineHCID 81531Diisopropylethylamine2×HCID 66603748(2'-Ethylaminomethyl-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

Product 1

HCID 66604003[2'-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To (2′-ethylaminomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester (0.207 g, 0.54 mmol) in CH2Cl2 (2 mL) at 0° C. was added diisopropylethylamine (0.21 mL, 1.19 mmol), followed by phosgene (20% in toluene; 0.34 mL, 0.65 mmol), and the reaction was stirred for 2 hours at 0° C. Benzylamine (0.09 mL, 0.81 mmol) was then added, and the reaction was stirred for 15 minutes. Triethylamine (0.1 mL, 0.72 mmol) was added, and the reaction was stirred for 1 hour. Additional benzylamine (0.09 mL, 0.81 mmol) and diisopropylethylamine (0.21 mL, 1.19 mmol) were added, and the reaction was stirred for 3 hours, until no starting material was seen by analytical LCMS. The mixture was partitioned between H2O and CH2Cl2, and the aqueous layer was separated and extracted twice with CH2Cl2. The combined organic layers were dried and concentrated, and the residue was purified by silica gel chromatography (20-40% EtOAc in hexanes) to give the title compound.

Workup

  1. stirringthe reaction was stirred for 15 minutes
  2. stirringthe reaction was stirred for 1 hour
  3. stirringthe reaction was stirred for 3 hours, until no starting material
  4. customThe mixture was partitioned between H2O and CH2Cl2
  5. customthe aqueous layer was separated
  6. extractionextracted twice with CH2Cl2
  7. customThe combined organic layers were dried
  8. concentrationconcentrated
  9. customthe residue was purified by silica gel chromatography (20-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a17ed1553d904805b3156160835e2a63
Source dataset
uspto-grants-2013_01
Patent number
US08362044B2

Reaction notes

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