Sodium hydride → HCID 178476294、化合物

HRID 1766889ノート

反応式

HRID 1766889 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([S:12][C@@H:13]1[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11].[H-].[Na+].[C:41]([O:44][CH2:45][CH2:46][CH2:47][C:48](=[O:50])Cl)(=[O:43])[CH3:42].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[C:41]([O:44][CH2:45][CH2:46][CH2:47][C:48]([O:38][C@:9]([C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([S:12][C@@H:13]1[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11])=[O:50])(=[O:43])[CH3:42]

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 123262134-Chloro-oxobutyl acetateHCID 178462432HCID 178462432、化合物

生成物 1

HCID 178476294HCID 178476294、化合物収率 49.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (1.10 g, 2.03 mmol) obtained from Reference example 1 was dissolved in N,N-dimethylformamide (5 ml), and then sodium hydride (ca. 50 mg, 2.1 mmol) was added thereto at room temperature. The mixture was stirred for 15 minutes, then 4-chloro-oxobutyl acetate (330 mg, 2.0 mmol) obtained from Example 12-(1) was added thereto, and the resulting mixture was stirred for another 1 hour. The mixture was diluted with ethyl acetate, and a saturated aqueous solution of ammonium chloride was poured thereinto. The organic layer was separated, then washed successively with an aqueous solution of sodium hydrogen carbonate and with an aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained crude compound was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d. ×600 mm) and JAIGEL-2H (20 mm i.d. ×600 mm) connected in series for use; solvent, chloroform] to afford the title compound (662 mg, 49% yield) as a colorless amorphous solid.

後処理

  1. customat room temperature
  2. stirringthe resulting mixture was stirred for another 1 hour
  3. customThe organic layer was separated
  4. washwashed successively with an aqueous solution of sodium hydrogen carbonate and with an aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe obtained crude compound
  8. customwas purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d. ×600 mm) and JAIGEL-2H (20 mm i.d. ×600 mm) connected in series for use; solvent, chloroform]

出典と根拠

ORDレコード
ord-ed5f07c5a430436fa853f253853186a5
出典データセット
uspto-grants-2007_06
特許番号
US07230023B2

反応ノート

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