Iodine → HCID 20796135, compound

HRID 916031Notes

Reaction equation

HRID 916031 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5]([OH:22])([C:18]([F:21])([F:20])[F:19])[CH2:6][C:7]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[O:16][CH3:17])=[CH2:8])[CH3:2].II.I[CH2:27]I>CCOCC.CCOC(C)=O.[Cu].[Zn]>[CH2:1]([O:3][C:4](=[O:23])[C:5]([CH2:6][C:7]1([C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[O:16][CH3:17])[CH2:27][CH2:8]1)([OH:22])[C:18]([F:19])([F:20])[F:21])[CH3:2]

Participants

7

Reactant 3

HCID 807IodineHCID 6346DiiodomethaneHCID 207961364-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl ester

Product 1

HCID 20796135HCID 20796135, compoundYield 76.6%

Reagents, catalysts & solvents 3

HCID 10290809Zinc copper coupleCatalystHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 620 mg (1.84 mmol) of 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-2-trifluoromethylpent-4-enoic acid ethyl ester, 475 mg zinc copper couple, and an iodine crystal in anhydrous ether in a sealed tube warmed to 55° C. was added dropwise 500 μL (6.20 mmol) of diiodomethane. The reaction was monitored by TLC in dichloromethane-hexanes (1:1) or ether-hexanes (2:8). After 18 hours, the mixture was cooled, diluted with EtOAc and filtered through diatomaceous earth. The filtrate was washed with three 10 mL portions of 1 N aqueous HCl, 10 mL of brine, three 10 mL portions of saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated. The crude material was adsorbed onto silica gel and chromatographed on silica gel using ether-hexanes (0:100, then 1:99, then 2:98) to afford 494 mg (76%) of 3,3,3-trifluoro-2-[1-(5-fluoro-2-methoxyphenyl)cyclopropylmethyl]-2-hydroxypropionic acid ethyl ester.

Workup

  1. temperaturethe mixture was cooled
  2. filtrationfiltered through diatomaceous earth
  3. washThe filtrate was washed with three 10 mL portions of 1 N aqueous HCl, 10 mL of brine, three 10 mL portions of saturated aqueous sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on silica gel

Sources & evidence

ORD record
ord-c97e289475ce4752aab695deed24748b
Source dataset
uspto-grants-2007_09
Patent number
US07268152B2

Reaction notes

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