2-(2-Fluorophenyl)ethylamine → (3-{[2-(2-Fluoro-phenyl)-ethylamino]-methyl}-4-methoxy-phenyl)-acetic acid methyl ester

HRID 553297Notes

Reaction equation

HRID 553297 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][NH2:10].[CH:11]([C:13]1[CH:14]=[C:15]([CH2:21][C:22]([OH:24])=[O:23])[CH:16]=[CH:17][C:18]=1[O:19][CH3:20])=O.[C:25](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH3:25][O:24][C:22](=[O:23])[CH2:21][C:15]1[CH:16]=[CH:17][C:18]([O:19][CH3:20])=[C:13]([CH2:11][NH:10][CH2:9][CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH:14]=1

Participants

5

Reactant 3

HCID 6433572-(2-Fluorophenyl)ethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 23025459(3-Formyl-4-methoxy-phenyl)-acetic acid

Product 1

HCID 67165931(3-{[2-(2-Fluoro-phenyl)-ethylamino]-methyl}-4-methoxy-phenyl)-acetic acid methyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(2-Fluorophenyl)ethylamine (180 mg) in dichloromethane (5 mL) was added to (3-formyl-4-methoxy-phenyl)-acetic acid (260 mg). After 30 minutes, sodium triacetoxyborohydride (0.5 g) was added. After a further 2.5 hours, the reaction mixture was evaporated and the residue loaded onto a conditioned SCX cartridge (10 g Varian). The cartridge was washed with methanol (50 mL) and then eluted with a mixture of methanol/0.880 ammonia solution [4:1] (50 mL). The elution fraction was concentrated, the residue was dissolved in methanol (100 mL) and tri-methylchlorosilane (2 mL) added. After 18 hours, the reaction mixture was evaporated and the residue purified on silica, eluting iso-hexane/ethyl acetate [4:1 to 1:1 to 0:1]+1% triethylamine, to give the subtitle compound as an oil (0.30 g).

Workup

  1. waitAfter a further 2.5 hours
  2. customthe reaction mixture was evaporated
  3. washThe cartridge was washed with methanol (50 mL)
  4. washeluted with a mixture of methanol/0.880 ammonia solution [4:1] (50 mL)
  5. concentrationThe elution fraction was concentrated
  6. dissolutionthe residue was dissolved in methanol (100 mL)
  7. additiontri-methylchlorosilane (2 mL) added
  8. waitAfter 18 hours
  9. customthe reaction mixture was evaporated
  10. customthe residue purified on silica
  11. washeluting iso-hexane/ethyl acetate [4:1 to 1:1 to 0:1]+1% triethylamine

Sources & evidence

ORD record
ord-c22fde2850814a238098d9997ddc0a12
Source dataset
uspto-grants-2011_05
Patent number
US07951954B2

Reaction notes

Loading…