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

HRID 547858ノート

反応式

HRID 547858 の反応式
[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]

参加物

5

反応物 4

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

生成物 1

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

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-9efa873c014241219b8b54b09ab26152
出典データセット
uspto-grants-2011_05
特許番号
US07939569B1

反応ノート

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