Tri-o-tolylphosphine → diisopropyl (2S,3R)-2-hydroxy-3-{(2E)-3-[4-(trifluoromethoxy)phenyl]-2-propenyl}butanedioate

HRID 888230Notes

Reaction equation

HRID 888230 reaction equation
[CH2:1]([C@H:4]([C@H:11]([OH:18])[C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])[C:5]([O:7][CH:8]([CH3:10])[CH3:9])=[O:6])[CH:2]=[CH2:3].Br[C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC#N.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:18][C@@H:11]([C@@H:4]([CH2:1]/[CH:2]=[CH:3]/[C:20]1[CH:21]=[CH:22][C:23]([O:26][C:27]([F:28])([F:29])[F:30])=[CH:24][CH:25]=1)[C:5]([O:7][CH:8]([CH3:10])[CH3:9])=[O:6])[C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13]

Participants

6

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 59875729diisopropyl (2R,3S)-2-allyl-3-hydroxybutanedioate2×

Product 1

HCID 58488014diisopropyl (2S,3R)-2-hydroxy-3-{(2E)-3-[4-(trifluoromethoxy)phenyl]-2-propenyl}butanedioateYield 86.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of diisopropyl (2R,3S)-2-allyl-3-hydroxybutanedioate (Intermediate 2a, 5.0 g; 19.4 mmol; 1.0 eq.), TEA (6.23 mL; 46.5 mmol; 2.4 eq.) in CH3CN (50.0 mL) was added 1-bromo-4-(trifluoromethoxy)benzene (5.13 g; 21.3 mmol; 1.1 eq.). To this solution was added a sonicated mixture of tri-o-tolylphosphine (0.59 g; 1.94 mmol; 0.10 eq.) and palladium(II) acetate (43.46 mg; 0.19 mmol; 0.01 eq.) in CH3CN (4 mL). The reaction was stirred at 80° C. for 14 h, cooled to RT and the solvents were evaporated (rotavap). The residue was taken up in EtOAc and washed with an aqueous saturated solution of NH4Cl, an aqueous saturated solution of NaHCO3 and then with an aqueous saturated solution of NaCl and dried over MgSO4. Evaporation of the solvent gave an oil. Purification by chromatography (SiO2, gradient from 10/90 EtOAc/c-hex to 100/0 EtOAc/c-hex in 30 min.) gave a colorless oil (6.98 g, 86.2%). M+(ESI): 419.2; M−(ESI): 417.0.

Workup

  1. additionTo this solution was added
  2. temperaturecooled to RT
  3. customthe solvents were evaporated (rotavap)
  4. washwashed with an aqueous saturated solution of NH4Cl
  5. dry with materialan aqueous saturated solution of NaHCO3 and then with an aqueous saturated solution of NaCl and dried over MgSO4
  6. customEvaporation of the solvent
  7. customgave an oil
  8. customPurification by chromatography (SiO2, gradient from 10/90 EtOAc/c-hex to 100/0 EtOAc/c-hex in 30 min.)

Sources & evidence

ORD record
ord-79cc589773674b9790324246d32cd10e
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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