Sodium hydride → HCID 178476294, compound

HRID 1766889Notes

Reaction equation

HRID 1766889 reaction equation
[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]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 123262134-Chloro-oxobutyl acetateHCID 178462432HCID 178462432, compound

Product 1

HCID 178476294HCID 178476294, compoundYield 49.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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]

Sources & evidence

ORD record
ord-ed5f07c5a430436fa853f253853186a5
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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