Sodium hydride → HCID 178459923, compound

HRID 1766887Notes

Reaction equation

HRID 1766887 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+].[CH2:41]([O:44][C:45]([O:47][CH2:48][CH2:49][CH2:50][C:51](Cl)=[O:52])=[O:46])[CH:42]=[CH2:43].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH2:41]([O:44][C:45]([O:47][CH2:48][CH2:49][CH2:50][C:51]([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:52])=[O:46])[CH:42]=[CH2:43]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178625384-(Allyloxycarbonyloxy)butyryl chlorideHCID 178462432HCID 178462432, compound

Product 1

HCID 178459923HCID 178459923, compoundYield 75.1%

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 (570 mg, 1.05 mmol) obtained from Example Reference example 1 was dissolved in N,N-dimethylformamide (3 ml), and sodium hydride (ca. 30 mg, 1.3 mmol) was added thereto at room temperature. The mixture was stirred for 1 hour, then 4-(allyloxycarbonyloxy)butyryl chloride (250 mg, 1.21 mmol) obtained from Example 11-(2) was added thereto, and the mixture was stirred further for 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, washed with an aqueous solution of sodium hydrogen carbonate and then with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue 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 (562 mg, 75% yield) as a colorless amorphous solid.

Workup

  1. customat room temperature
  2. stirringthe mixture was stirred further for 1 hour
  3. customThe organic layer was separated
  4. washwashed with an aqueous solution of sodium hydrogen carbonate
  5. dry with materialwith an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue 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]

Sources & evidence

ORD record
ord-b5513773b2ee4d04bc932eae3c057479
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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