Hydrochloric Acid → HCID 178519898, compound

HRID 638786Notes

Reaction equation

HRID 638786 reaction equation
[OH:1][C:2]1[CH:8]2[CH2:9][CH:5]([CH2:6][CH2:7]2)[C:4](=[O:10])[C:3]=1[C:11]([C:13]1[C:14]([CH2:23][OH:24])=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=1)=[O:12].[H-].[Na+].[CH2:27]([CH:29]1[O:31][CH2:30]1)Br.Cl>CN(C)C=O.C(OCC)(=O)C>[OH:10][C:4]1[CH:5]2[CH2:9][CH:8]([CH2:7][CH2:6]2)[C:2](=[O:1])[C:3]=1[C:11]([C:13]1[C:14]([CH2:23][O:24][CH2:27][CH:29]2[CH2:30][O:31]2)=[N:15][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:17][CH:18]=1)=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 18430EpibromohydrinHCID 24758Sodium hydrideHCID 178519897HCID 178519897, compound

Product 1

HCID 178519898HCID 178519898, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1.5 g of 4-hydroxy-3-(2-hydroxymethyl-6-trifluoromethylpyridine-3-carbonyl)-bicyclo[3.2.1]oct-3-en-2-one are dissolved in 15 ml of dimethylformamide and, at room temperature, treated with 0.4 g of sodium hydride (80% suspension in oil, 0.013 mol), a little at a time. After 15 minutes at a temperature of 22° C., 3 ml (0.036 mol) of epibromohydrin are added dropwise, and the reaction mixture is stirred at this temperature for another 18 hours. Ethyl acetate is then added, and the mixture is acidified to pH 3 using 10% hydrochloric acid and extracted with ethyl acetate. The organic phase is dried over sodium sulfate and the crude product is purified chromatographically (mobile phase: toluene/ethyl alcohol/dioxane/triethylamine/water 100:40:20:20:5 parts by volume). This gives the title compound (triethylamine salt) in the form of a yellowish resin, which is released similarly to example H4. Trituration with hexane gives 600 mg of pure 4-hydroxy-3-2-oxiranylmethoxymethyl-6-trifluoromethylpyridin-3-carbonyl)bicyclo[3.2.1]oct-3-en-2-one of melting point 54-56° C.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. customthe crude product is purified chromatographically (mobile phase: toluene/ethyl alcohol/dioxane/triethylamine/water 100:40:20:20:5 parts by volume)

Sources & evidence

ORD record
ord-41369830a17341bb850e370f6e08fd93
Source dataset
uspto-grants-2010_04
Patent number
US07691785B2

Reaction notes

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