Sulfuric Acid → HCID 21110477, compound

HRID 1766923Notes

Reaction equation

HRID 1766923 reaction equation
[P:1]([O:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[CH2:23][OH:24])[CH:16]=[CH:15][CH:14]=1)([O:7][CH2:8][CH:9]=[CH2:10])([O:3][CH2:4][CH:5]=[CH2:6])=[O:2].CC(C)=[O:27].OS(O)(=O)=O.O=[Cr](=O)=O.S(=O)(=O)(O)O.CC(O)C>CC(C)=O.O>[CH2:4]([O:3][P:1]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[C:21]([C:23]([OH:27])=[O:24])=[CH:20][CH:19]=[CH:18]2)([O:7][CH2:8][CH:9]=[CH2:10])=[O:2])[CH:5]=[CH2:6]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 3776IsopropanolHCID 46834506HCID 46834506, compoundHCID 131709961Jones' reagent

Product 1

HCID 21110477HCID 21110477, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of diallyl [8-(hydroxymethyl)-1-naphthyl]methyl phosphate (1.1492 g, 3.30 mmol) in acetone (20 ml) obtained from Example 25-(2) was added Jones reagent (a mixture of chromic anhydride (5.34 g) and concentrated sulfuric acid (4.6 ml) diluted with water to 20 ml total volume; 5 ml, ca. 13.2 mmol). The reaction mixture was stirred at room temperature for 90 minutes, then cooled to 0° C., and then 2-propanol (0.5 ml) was added thereto to stop the reaction. The insoluble material was filtered off, and the solvent was distilled off under reduced pressure to give an oily residue. The residue was dried using a vaccum pump, and then subjected to chromatography on a silica gel (30 g) column (eluent; ethyl acetate:dichloromethane=1:10˜3:10) to afford crude 8-[[bis(allyloxy)phosphoryl]oxymethyl]-1-naphthoic acid as an oil. The product was dissolved in dichloromethane (10 ml), and then oxalyl chloride (1 g, 7.88 mmol) and N,N-dimethylformamide (15 μl) were added thereto. After the mixture was stirred at room temperature for 30 minutes, crude 8-[[bis(allyloxy)phosphoryl]oxymethyl]-1-naphthoyl chloride was obtained according to a similar procedure to that described in Example 1-(12). According to a similar procedure to that described in Example 1-(12), 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 (542.7 mg, 1.0 mmol) described in Reference example 1, sodium hydride (55% dispersion in mineral oil; 43 mg, 1.0 mmol), and the crude 8-[[bis(allyloxy)phosphoryl]oxymethyl]-1-naphthoyl chloride obtained above were reacted in tetrahydrofuran (5 ml) and the reaction mixture was worked up to afford, after extraction, the title compound as a crude oil. The crude oil was subjected to chromatography on a silica gel (50 g) column (eluent; ethyl acetate:hexane=1:1˜5:1) to afford the title compound (459.2 mg, 52% yield) as a pale yellow amorphous solid.

Workup

  1. temperaturecooled to 0° C.
  2. customthe reaction
  3. filtrationThe insoluble material was filtered off
  4. distillationthe solvent was distilled off under reduced pressure
  5. customto give an oily residue
  6. customThe residue was dried

Sources & evidence

ORD record
ord-e1aa69ab903b4fed8ca81de397cb091e
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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