Phosphate → HCID 178462430, compound

HRID 1766898Notes

Reaction equation

HRID 1766898 reaction equation
N1([C:6]([O:8][C@:9]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=2[F:45])([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:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][C:24]=3[F:31])[O:15][CH2:14]2)[CH3:11])=[O:7])C=CN=C1.[Si:46]([O:63][CH2:64][CH2:65][OH:66])([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.P([O-])([O-])([O-])=O>ClCCl.CC(C)([O-])C.[K+]>[C:6](=[O:7])([O:8][C@:9]([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1[F:45])([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:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11])[O:66][CH2:65][CH2:64][O:63][Si:46]([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

6

Reactant 3

HCID 1061PhosphateHCID 151562692-((tert-Butyldiphenylsilyl)oxy)ethanolHCID 178462428HCID 178462428, compound

Product 1

HCID 178462430HCID 178462430, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 23665647Potassium tert-butoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

(1R,2R)-2-[[trans-2-[(1E,3E)-4-(4-Cyano-2-fluorophenyl)-1,3-butadienyl]-1,3-dioxan-5-yl]thio]-1-(2,4-difluorophenyl)-1-[(1H-1,2,4-triazol-1-yl)methyl]propyl imidazole-1-carboxylate (637 mg, 1.00 mmol) obtained from Example 15-(1) and the crude 2-[(tert-butyldiphenylsilyl)oxy]ethanol (315 mg, ca. 1.05 mmol) obtained from Example 15-(2) were dissolved in dichloromethane (3 ml), and potassium tert-butoxide (5 mg) was added thereto. The mixture was heated under reflux for 15 minutes with stirring. After cooling, a phosphate buffer solution (pH 7) was poured into the mixture, and the reaction product was extracted with ethyl acetate. The organic layer was 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 (631.4 mg, 73% yield) as a colorless amorphous solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 15 minutes
  3. temperatureAfter cooling
  4. extractionthe reaction product was extracted with ethyl acetate
  5. dry with materialThe organic layer was 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-53349c4320cc47a6bee39377e65ac0ab
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

Loading…