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

HRID 1919960Notes

Reaction equation

HRID 1919960 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(CC)CC)C.[CH2:36]([N:43]=[C:44]=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>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:44]([NH:43][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:45])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76639Benzyl isocyanateHCID 66604101(2'-Ethylaminomethyl-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester

Product 1

HCID 66603809[2'-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Alternative synthesis: To (2′-ethylaminomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester (prepared as described in Example 1, Step 1 but using EtOH in place of MeOH; 44.9 g, 0.114 mol) in CH2Cl2 (450 mL) at room temperature was added triethylamine (24 mL, 0.17 mol), followed by benzylisocyanate (16.7 mL, 0.136 mol), and the reaction was stirred for 2 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 with CH2Cl2. The combined organic layers were dried (MgSO4) and concentrated, and the residue was purified by silica gel chromatography (0-60% EtOAc in hexanes) to give the [2′-(3-benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid ethyl ester. Hydrolysis of the ethyl ester according to the procedure described in Example 1, Step 7 provided [2′-(3-benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid.

Workup

  1. customAlternative synthesis
  2. customThe mixture was partitioned between H2O and CH2Cl2
  3. customthe aqueous layer was separated
  4. extractionextracted with CH2Cl2
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel chromatography (0-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c5bd4f00f3fd4c56acdb54ece0fab6b2
Source dataset
uspto-grants-2012_05
Patent number
US08168678B2

Reaction notes

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