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

HRID 1665253Notes

Reaction equation

HRID 1665253 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][CH:25]=3)[C:20](O)=[O:21])=[CH:11][CH:10]=2)=[C:4]([O:26][CH3:27])[CH:3]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.Cl.[CH2:59]([O:61][C:62](=[O:66])[CH2:63][NH:64][CH3:65])[CH3:60]>C(Cl)Cl.O.CCOC(C)=O>[CH2:59]([O:61][C:62](=[O:66])[CH2:63][N:64]([C:20](=[O:21])[C:19]1[CH:23]=[CH:24][CH:25]=[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:26][CH3:27])=[CH:14][CH:13]=2)[CH:18]=1)[CH3:65])[CH3:60]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 181649HOAtHCID 582711913-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-benzoic acid

Product 1

HCID 67152371{[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-methyl-amino}-acetic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-benzoic acid (20 g, 54 mmol), DIEA (38 mL, 216 mmol), EDCI (15.47 g, 81 mmol) and HOAT (11 g, 81 mmol) in methylene chloride (800 mL) was stirred at room temperature for 1 h, followed by addition of N-methyl glycine ethyl ester hydrochloride (12.44 g, 81 mmol). The resulting mixture was stirred at room temperature for 24 h, then treated with EtOAc (1.5 L) and water (1.5 L). The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The oily residue was purified by column (0-35% EtOAc in hexane) to give {[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-methyl-amino}-acetic acid ethyl ester, 17 g (67%). LC-MS (ES) calculated for C26H25F2NO5, 469; found m/z 470 [M+H]+.

Workup

  1. customThe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe oily residue was purified by column (0-35% EtOAc in hexane)

Sources & evidence

ORD record
ord-7a4928e636ed47bb97660d8a606df5bf
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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