Boron trifluoride etherate → Methyl 4-(4-bromo-2,6-dimethylphenyl)-3-hydroxybutanoate

HRID 708812Notes

Reaction equation

HRID 708812 reaction equation
CC(C[AlH]CC(C)C)C.[Br:10][C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([CH2:18][C:19]([O:21]C)=O)=[C:13]([CH3:23])[CH:12]=1.[Si]([O:31][C:32]([O:34][CH3:35])=[CH2:33])(C(C)(C)C)(C)C.B(F)(F)F.CCOCC>C(Cl)Cl>[Br:10][C:11]1[CH:12]=[C:13]([CH3:23])[C:14]([CH2:18][CH:19]([OH:21])[CH2:33][C:32]([O:34][CH3:35])=[O:31])=[C:15]([CH3:17])[CH:16]=1

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 14487Diisobutylaluminum hydrideHCID 45644911-(tert-Butyldimethylsilyloxy)-1-methoxyetheneHCID 22889389Methyl 2-(4-bromo-2,6-dimethylphenyl)acetate

Product 1

HCID 118098683Methyl 4-(4-bromo-2,6-dimethylphenyl)-3-hydroxybutanoateYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIBAL-H (8.66 mL, 12.99 mmol) was added dropwise to a solution of methyl 2-(4-bromo-2,6-dimethylphenyl)acetate (3.18 g, 12.37 mmol) in CH2Cl2 (60 mL) at −78° C. and stirred for 1 h. 1-(tert-Butyldimethylsilyloxy)-1-methoxyethene (4.05 mL, 18.55 mmol) followed by BF3.OEt2 (1.959 mL, 15.46 mmol) were added. The reaction was stirred at −78° C. for 20 min and then allowed to warm to rt. The reaction was quenched by the addition of 10 mL of 1.0 M HCl, extracted with dichloromethane. The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography (loading in chloroform, 0% to 50% ethyl acetate in hexane over 15 min using a 40 g silica gel cartridge) to yield 2A (2.5 g, 8.30 mmol, 67.1% yield) as a clear oil. 1H NMR (500 MHz, chloroform-d) δ ppm 7.18 (2H, s), 4.20-4.28 (1H, m), 3.72 (3H, s), 2.91 (1H, dd, J=14.03, 8.25 Hz), 2.72-2.78 (2H, m), 2.53-2.57 (2H, m), 2.55 (2H, dd, J=40.03, 6.19 Hz), 2.33 (6H, s), 1.58 (2H, br. s.).

Workup

  1. additionwere added
  2. stirringThe reaction was stirred at −78° C. for 20 min
  3. customThe reaction was quenched by the addition of 10 mL of 1.0 M HCl
  4. extractionextracted with dichloromethane
  5. washThe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (loading in chloroform
  9. wait0% to 50% ethyl acetate in hexane over 15 min using

Sources & evidence

ORD record
ord-2c782255caeb48fa9988cb2cc51e72ca
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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