Water → 2-Biphenyl-3-yl-4-methylpentenoic acid

HRID 968336

Reaction equation

HRID 968336 reaction equation
[C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([OH:10])=[O:9])[CH:2]=1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:26][C:27]([CH3:29])=[CH2:28].O>O1CCCC1.CO.ClCCl>[C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=[CH:26][CH:27]([CH3:29])[CH3:28])[C:8]([OH:10])=[O:9])[CH:2]=1

Participants

7

Reactant 4

HCID 962WaterHCID 321533-Biphenylylacetic acidHCID 3577853-Bromo-2-methyl-1-propeneHCID 2724682Lithium diisopropylamide

Product 1

HCID 697345682-Biphenyl-3-yl-4-methylpentenoic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of biphenyl-3-yl acetic acid (7.0 g, 33 mmol) in anhydrous tetrahydrofuran (84 mL) was added dropwise to a solution of lithium diisopropyl amide (36.4 mL, 2M solution in hexanes) in anhydrous tetrahydrofuran (84 mL) at −78° C. The mixture was allowed to warm to 0° C. and stirred for 40 min. The mixture was then cooled to −78° C. and 3-bromo-2-methylpropene (4.97 mL) rapidly added. The mixture was stirred for 1 h at −78° C. then water (28 mL) added and the organics removed under reduced pressure. The mixture was then acidified with hydrochloric acid (6M, 14 ml), extracted with ethyl acetate (3×100 ml), dried (MgSO4) and evaporated under reduced pressure to afford a residue. Flash chromatography of the residue over silica (400 g) using methanol:dichloromethane (3:97) as the eluent afforded impure 2-biphenyl-3-yl-4-methylpentenoic acid (8.3 g). Flash chromatography over silica (400 g) using methanol:dichloromethane (1.5:98.5) afforded pure 2-biphenyl-3-yl-4-methylpent-4-enoic acid, yield 5.27 g, (60%), TLC (single UV spot, Rf=0.28, 5% methanol in dichloromethane), analytical HPLC Rt=19.99 min, HPLC-MS (single main UV peak with Rt=9.57 min, 267.1 [M+H]+).

Workup

  1. temperatureThe mixture was then cooled to −78° C.
  2. stirringThe mixture was stirred for 1 h at −78° C.
  3. customthe organics removed under reduced pressure
  4. extractionextracted with ethyl acetate (3×100 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customto afford a residue

Sources & evidence

ORD record
ord-73bb06f1a3a74b6cae80c65bae156323
Source dataset
uspto-grants-2005_10
Patent number
US06958358B2

Linked notes

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