Acetyl chloride → {Acetyl-[3-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenyl]-amino}-acetic acid ethyl ester

HRID 547858Notes

Reaction equation

HRID 547858 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:22]=3[O:29][CH3:30])=[CH:17][CH:16]=2)[CH:8]=1)[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(N(C(C)C)CC)(C)C.[C:51](Cl)(=[O:53])[CH3:52]>>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][N:6]([C:51](=[O:53])[CH3:52])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:22]=3[O:29][CH3:30])=[CH:19][CH:20]=2)[CH:8]=1)[CH3:2]

Participants

5

Reactant 4

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 2733832Lithium HexamethyldisilazideHCID 67153766[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester

Product 1

HCID 67153758{Acetyl-[3-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenyl]-amino}-acetic acid ethyl ester

Procedure

To a vial containing [3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester (47 mg, 0.11 mmol) dissolved in dimethylformide (1 mL) was added lithium bis(trimethylsilyl)amide (1 M in THF, 0.13 mL, 0.13 mmol), diisopropylethyl amine (0.238 mL, 1.3 mmol) and acetyl chloride. The reaction was stirred at room temperature overnight. Reaction was filtered and purified by HPLC with increasing concentration of acetonitrile in water with 0.1% trifluoroacetic acid to yield {acetyl-[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenyl]-amino}-acetic acid ethyl ester as a clear film (10 mg, 21%). LC-MS (ES) calculated for C26H25F2NO5, 469.17; found m/z 470 [M+H]+.

Workup

  1. dissolutiondissolved in dimethylformide (1 mL)
  2. customReaction
  3. filtrationwas filtered
  4. custompurified by HPLC
  5. temperaturewith increasing concentration of acetonitrile in water with 0.1% trifluoroacetic acid

Sources & evidence

ORD record
ord-9efa873c014241219b8b54b09ab26152
Source dataset
uspto-grants-2011_05
Patent number
US07939569B1

Reaction notes

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