Phosphate → HCID 178460582, compound

HRID 1766947Notes

Reaction equation

HRID 1766947 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][P:45]([O:51][CH2:52][C:53]1[CH:57]=[CH:56][S:55][C:54]=1[C:58](Cl)=[O:59])([O:47][CH2:48][CH:49]=[CH2:50])=[O:46])[CH:42]=[CH2:43].P([O-])([O-])([O-])=O>COCCOC>[CH2:48]([O:47][P:45]([O:51][CH2:52][C:53]1[CH:57]=[CH:56][S:55][C:54]=1[C:58]([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:59])([O:44][CH2:41][CH:42]=[CH2:43])=[O:46])[CH:49]=[CH2:50]

Participants

6

Reactant 4

HCID 1061PhosphateHCID 24758Sodium hydrideHCID 21110456HCID 21110456, compoundHCID 178462432HCID 178462432, compound

Product 1

HCID 178460582HCID 178460582, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 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 (699.1 mg, 1.29 mmol) described in Reference example 1 in 1,2-dimethoxyethane (10 ml) was cooled to 0° C., and sodium hydride (55% dispersion in mineral oil; 67.5 mg, 1.55 mmol) was added thereto, and the resulting mixture was stirred at room temperature for 3 hours. To the mixture was added a solution of the crude 3-[[bis(allyloxy)phosphoryl]oxymethyl]-2-thenoyl chloride obtained above in 1,2-dimethoxyethane (2 ml), and the mixture was stirred at room temperature for 20 minutes and cooled to 0° C., then a phosphate buffer solution (pH 7) was added to the reaction mixture to stop the reaction, and the product was extracted with ethyl acetate. The crude product was subjected to chromatography on a silica gel (40 g) column (eluent; ethyl acetate:hexane=3:2˜5:1) to give the title compound (520.6 mg, 48% yield) as a pale yellow amorphous solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 20 minutes
  2. temperaturecooled to 0° C.
  3. customthe reaction
  4. extractionthe product was extracted with ethyl acetate

Sources & evidence

ORD record
ord-5400db58f08a4ddf934055db56af7270
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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