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

HRID 547858노트

반응식

HRID 547858 반응식
[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]

참가 물질

5

반응물 4

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

생성물 1

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

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-9efa873c014241219b8b54b09ab26152
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07939569B1

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