Ethyl 3,3,3-trifluoro-2-oxopropanoate → HCID 90780200, compound

HRID 1362527Notes

Reaction equation

HRID 1362527 reaction equation
[F:1][C:2]1[C:3]([CH3:14])=[C:4]([O:12][CH3:13])[C:5]([C:8](=[CH2:11])[CH2:9][CH3:10])=[CH:6][CH:7]=1.[F:15][C:16]([F:25])([F:24])[C:17](=[O:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19]>ClCCl.FC(F)(F)CO.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:9][CH3:10])[CH2:11][C@:17]([OH:23])([C:16]([F:24])([F:25])[F:15])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:4]([O:12][CH3:13])[C:3]=1[CH3:14]

Participants

6

Reactant 2

HCID 2737239Ethyl 3,3,3-trifluoro-2-oxopropanoateHCID 66969520HCID 66969520, compound

Product 1

HCID 90780200HCID 90780200, compoundYield 34.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
0 °C

Procedure

5.7 g (29.3 mmol) of 3-fluoro-2-methyl-6-(1-methylenepropyl)anisole, 7.7 ml (170 mmol) of ethyl trifluoropyruvate and 15 g of molecular sieve are admixed dropwise at 0° C. over 30 minutes with 0.76 g (0.88 mmol) of [Cu(R,R)-2,2-bis(4,5-dihydro-4-tert-butyloxazolin-2-yl)propane)(H2O)2]((SbF6)2, in 38 ml of dichloromethane. The reaction mixture is stirred at 0° C. for 16 hours and the reaction mixture is purified by means of column chromatography on silica gel (hexane/ethyl acetate 0-20%). This gives 8.7 g of ethyl (R)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hex-4-enoate as an E/Z mixture with an enantiomeric excess of greater than 80%, and in this way 13.9 of crude E/Z-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-(trifluoromethyl)hex-4-ene-1,2-diol. 4.0 g (11 mmol) of ethyl (2R,4E/Z)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hex-4-enoate are dissolved in 180 ml of 2,2,2-trifluoroethanol and the solution is admixed with 400 mg of palladium on carbon (10%). The suspension is shaken under a hydrogen atmosphere at 100 bar until reaction is complete. The mixture is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. The concentrated crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 15%) to give 3.7 g (10 mmol) of ethyl (2R,4R/S)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanoate as a diastereomer mixture. 3.7 g (10 mmol) of ethyl (2R,4R/S)-4-(4-fluoro-2-methoxy-3-methylphenyl)-2-hydroxy-2-(trifluoromethyl)hexanoate are cooled to −15° C. in 132 ml of diethyl ether and admixed over 10 minutes with solid lithium aluminum hydride, 1.03 g (27.3 mmol), in portions. The mixture is stirred at −10° C. for 3 hours, and ethyl acetate and water are added cautiously. The suspension is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate.

Workup

  1. customthe reaction mixture is purified by means of column chromatography on silica gel (hexane/ethyl acetate 0-20%)
  2. stirringThe suspension is shaken under a hydrogen atmosphere at 100 bar until reaction
  3. filtrationThe mixture is filtered through Celite
  4. washthe filter bed being rinsed thoroughly with ethyl acetate
  5. concentrationThe concentrated crude product
  6. customis purified by column chromatography on silica gel (hexane/ethyl acetate 15%)

Sources & evidence

ORD record
ord-de33454b19f445e69d7409ba94b1ecd8
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

Loading…