Triethylamine → {[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester

HRID 1665260Notes

Reaction equation

HRID 1665260 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=3[F:26])[C:20](O)=[O:21])=[CH:11][CH:10]=2)=[C:4]([O:27][CH3:28])[CH:3]=1.Cl.[CH2:30]([O:32][C:33](=[O:37])[CH2:34][NH:35][CH3:36])[CH3:31].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C>C(Cl)Cl>[CH2:30]([O:32][C:33](=[O:37])[CH2:34][N:35]([C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:25]([F:26])=[C:17]([CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([C:5]3[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=3[O:27][CH3:28])=[CH:14][CH:13]=2)[CH:18]=1)[CH3:36])[CH3:31]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 181649HOAtHCID 582711923-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid

Product 1

HCID 67152333{[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl esterYield 77.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-(4′,5′-difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid (0.3 g, 0.77 mmol) and N-methyl-glycine ethyl ester hydrochloride (0.7 g, 4.5 mmol) in methylene chloride (40 mL) was added HOAT (0.2 g, 1.46 mmol), EDCI (0.3 g, 1.56 mmol) and triethylamine (1.4 mL, 10 mmol). The mixture was stirred at room temperature for 3 hrs and extracted with methylene chloride and dilute hydrochloric acid. The organic layer was dried and concentrated. The residue was purified through flash column chromatography (80 g silica gel, 5% to 60% ethyl acetate in hexanes over 25 minutes) to give amorphous material as {[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester (0.29 g, 77%).

Workup

  1. extractionextracted with methylene chloride and dilute hydrochloric acid
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified through flash column chromatography (80 g silica gel, 5% to 60% ethyl acetate in hexanes over 25 minutes)

Sources & evidence

ORD record
ord-2b414125536f4b669eaced69d24f945b
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

Loading…