Phosgene → HCID 66606918, compound

HRID 1810396Notes

Reaction equation

HRID 1810396 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=2[CH2:24][NH:25][CH2:26][CH3:27])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].C(N(C(C)C)CC)(C)C.[C:38](Cl)(Cl)=[O:39].[NH2:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=1.C(N(CC)CC)C>C(Cl)Cl.O>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:16][C:15]=2[CH2:24][N:25]([CH2:26][CH3:27])[C:38]([NH:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=2)=[O:39])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]

Participants

8

Reactant 5

HCID 6371PhosgeneHCID 8471Triethylamine2×HCID 195092-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 66604101(2'-Ethylaminomethyl-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester

Product 1

HCID 66606918HCID 66606918, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(2′-Ethylaminomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester (0.203 g, 0.51 mmol) and diisopropylethylamine (0.22 mL, 1.28 mmol) were combined in CH2Cl2 (2 mL) and cooled to 0° C. Phosgene (20% in toluene; 0.41 mL, 0.77 mmol) was added, and the reaction was stirred for 2.5 hours. After warming to room temperature, 2-(aminomethyl)pyridine (0.08 mL, 0.77 mol) was added, followed by triethylamine (0.14 mL, 1.02 mmol), and the reaction was stirred for 30 minutes. Analytical LCMS indicated that some starting material was still present, so additional triethylamine (0.07 mL, 0.51 mmol) was added, and the reaction was stirred for 45 minutes. The mixture was diluted with CH2Cl2 and H2O, and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried and concentrated, and the residue was purified by silica gel chromatography (40-100% EtOAc in hexanes) to give the title compound.

Workup

  1. temperatureAfter warming to room temperature
  2. stirringthe reaction was stirred for 30 minutes
  3. stirringthe reaction was stirred for 45 minutes
  4. extractionthe aqueous layer was extracted twice with CH2Cl2
  5. customThe combined organic layers were dried
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel chromatography (40-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-66259333f2e6488dab48b824399d6453
Source dataset
uspto-grants-2013_01
Patent number
US08362044B2

Reaction notes

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