4-Bromophenetole → di-isopropyl (2R,3S)-2-[(2E)-3-(4-ethoxyphenyl)-2-propenyl]-3-hydroxybutanedioate

HRID 888168Notes

Reaction equation

HRID 888168 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].CCN(C(C)C)C(C)C.Br[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH3:37])=[CH:31][CH:30]=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>[CH2:36]([O:35][C:32]1[CH:33]=[CH:34][C:29](/[CH:3]=[CH:2]/[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:30][CH:31]=1)[CH3:37]

Participants

7

Reactant 4

HCID 685234-BromophenetoleHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59875729diisopropyl (2R,3S)-2-allyl-3-hydroxybutanedioate

Product 1

HCID 58488035di-isopropyl (2R,3S)-2-[(2E)-3-(4-ethoxyphenyl)-2-propenyl]-3-hydroxybutanedioateYield 97.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of diisopropyl (2R,3S)-2-allyl-3-hydroxybutanedioate (3.0 g; 11.6 mmol; 1.0 eq.) and DIEA (3.86 mL; 28.9 mmol; 2.4 eq.) in CH3CN (30.0 mL) was added 4-bromophenetole (2.0 mL; 13.9 mmol; 1.2 eq.). To this solution was added a mixture of tri-o-tolylphosphine (0.35 g; 1.16 mmol; 0.1 eq.) and palladium(II) acetate (0.03 g; 0.12 mmol; 0.01 eq.) in CH3CN (3.0 mL) which was sonicated before the addition to the reaction mixture. The reaction was stirred under argon at reflux for 2.5 h, cooled to RT and the solvents were evaporated under reduce pressure. The resulting residue was then taken up in EtOAc and washed with an aqueous saturated solution of NaCl. Evaporation of the solvent gave an oil (4.3 g). Purification by chromatography (SiO2, gradient from 20/80 EtOAc/c-hex to 100/0 EtOAc/c-hex) gave the title product as a colorless oil (4.41 g, 100%). M+(ESI): 379.3. 1H NMR (CDCl3, 300 MHz) δ 7.14 (d, J=8.6 Hz, 2H), 6.70 (d, J=8.6 Hz, 2H), 6.46 (d, J=15.6 Hz, 1H), 6.00-5.86 (m, 1H), 5.05-4.83 (m, 2H), 4.13 (dd, J=7.0 Hz, J=3.0 Hz, 1H), 3.90 (q, J=7.0 Hz, 2H), 3.10 (d, J=7.2 Hz, 1H), 2.89-2.78 (m, 1H), 2.70-2.55 (m, 1H), 2.52-2.35 (m, 1H), 1.27 (t, J=7.0 Hz, 3H), 1.22-1.00 (m, 12H).

Workup

  1. additionTo this solution was added
  2. customwas sonicated before the addition to the reaction mixture
  3. temperatureat reflux for 2.5 h
  4. customthe solvents were evaporated
  5. washwashed with an aqueous saturated solution of NaCl
  6. customEvaporation of the solvent

Sources & evidence

ORD record
ord-f14bfeaa79984d6ab861b0477deea83a
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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