Phosgene → HCID 66604437, compound

HRID 1810381Notes

Reaction equation

HRID 1810381 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].[OH:42][C:43]1[CH:50]=[CH:49][C:46]([CH2:47][NH2:48])=[CH:45][CH:44]=1.C(N(CC)CC)C>C(Cl)Cl>[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:48][CH2:47][C:46]2[CH:49]=[CH:50][C:43]([OH:42])=[CH:44][CH:45]=2)=[O:39])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 974724-Hydroxybenzylamine2×HCID 66604101(2'-Ethylaminomethyl-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester

Product 1

HCID 66604437HCID 66604437, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (2′-ethylaminomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester (0.59 g, 1.49 mmol) and diisopropylethylamine (0.65 mL, 3.73 mmol) in CH2Cl2 (6 mL) at 0° C. was added phosgene (20% in toluene; 1.2 mL, 2.24 mmol), and the reaction was stirred for 1 hour. 4-Hydroxybenzylamine (0.278 g, 2.24 mmol) and triethylamine (1 mL, 7.47 mmol) were then added, and the reaction was stirred for 2 hours. Analytical LCMS indicated the starting material was still present, so additional 4-hydroxybenzylamine (0.184 g, 1.49 mmol) was added, and the reaction was stirred for another 30 minutes. The mixture was partitioned between CH2Cl2 and H2O, and the organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound.

Workup

  1. stirringthe reaction was stirred for 2 hours
  2. stirringthe reaction was stirred for another 30 minutes
  3. customThe mixture was partitioned between CH2Cl2 and H2O
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-157433d1720e47379e24d9a677285e33
Source dataset
uspto-grants-2013_01
Patent number
US08362044B2

Reaction notes

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