Phosgene → HCID 66604437, compound

HRID 1919989Notes

Reaction equation

HRID 1919989 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. 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-f98dd3f8ff7649c6b625de62fdcd9c3f
Source dataset
uspto-grants-2012_05
Patent number
US08168678B2

Reaction notes

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