Phosphate → HCID 178462428, compound

HRID 1766896Notes

Reaction equation

HRID 1766896 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].[C:39](N1C=CN=C1)([N:41]1[CH:45]=[CH:44][N:43]=[CH:42]1)=[O:40].P([O-])([O-])([O-])=O>ClCCl.[H-].[Na+]>[N:41]1([C:39]([O:38][C@:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])([CH2:32][N:33]2[CH:37]=[N:36][CH:35]=[N:34]2)[C@H:10]([S:12][C@@H:13]2[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]3[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=3[F:31])[O:15][CH2:14]2)[CH3:11])=[O:40])[CH:45]=[CH:44][N:43]=[CH:42]1

Participants

6

Reactant 3

HCID 1061PhosphateHCID 682631,1'-CarbonyldiimidazoleHCID 178462432HCID 178462432, compound

Product 1

HCID 178462428HCID 178462428, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 24758Sodium hydrideCatalystHCID 6344DichloromethaneSolvent

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 (4.90 g, 9.03 mmol) described in Reference example 1 and 1,1′-carbonyldiimidazole (1.53 g, 9.44 mmol) were dissolved in dichloromethane (20 ml). To the mixture was added sodium hydride (55% dispersion in mineral oil; 10 mg, 2.3×10−4 mol), and the reaction mixture was heated under reflux for 3 hours with stirring. After cooling, a phosphate buffer solution (pH 7.4) was added thereto, and the product was extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel (120 g) column (eluent; ethyl acetate:hexane=1:1˜1:0) to afford the title compound (4.00 g, 70% yield) as a colorless amorphous solid.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperatureAfter cooling
  4. extractionthe product was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-1d00c442ba914392ba35835e03768ae2
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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