Phenethylamine → [6-Methoxy-2'-(phenethylamino-methyl)-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid methyl ester

HRID 1810362Notes

Reaction equation

HRID 1810362 reaction equation
[CH3:1][O:2][C:3](=[O:25])[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[CH:23]=O)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.[C:26]1([CH2:32][CH2:33][NH2:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][C:14]=2[CH2:23][NH:34][CH2:33][CH2:32][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 1001Phenethylamine2×HCID 5049666Sodium triacetoxyborohydride3×HCID 86633167(2'-Formyl-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

Product 1

HCID 66607670[6-Methoxy-2'-(phenethylamino-methyl)-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2′-formyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester (0.277 g, 0.79 mmol) and 2-phenylethylamine (0.15 mL, 1.18 mmol) in CH2Cl2 (4 mL) was added sodium triacetoxyborohydride (0.251 g, 1.18 mmol), and the reaction was stirred at room temperature for 2 hours. Analytical LCMS indicated that some starting material was still present, so additional 2-phenylethylamine (0.15 mL, 1.18 mmol) was added, along with acetic acid (1 drop), and the reaction was stirred overnight at room temperature. Analytical LCMS showed that starting material still remained, so additional sodium triacetoxyborohydride (0.260 g, 1.23 mmol) was added, and the reaction was stirred for 2.5 hours. Additional sodium triacetoxyborohydride (0.500 g, 2.36 mmol) was added, and the reaction was stirred for 1.5 hours, until no starting material was seen by analytical LCMS. The mixture was worked-up, and the residue was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound.

Workup

  1. stirringthe reaction was stirred overnight at room temperature
  2. stirringthe reaction was stirred for 2.5 hours
  3. stirringthe reaction was stirred for 1.5 hours, until no starting material
  4. customthe residue was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-dec2a183685849688c34eae33d3efe5a
Source dataset
uspto-grants-2013_01
Patent number
US08362044B2

Reaction notes

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