Iodine → 3,5-Bis-benzyloxy-4-(2-methyl-allyl)-benzoic acid tert-butyl ester

HRID 1643706Notes

Reaction equation

HRID 1643706 reaction equation
II.C([Mg]Br)(C)C.[Li]CCCC.[C:13]([O:17][C:18](=[O:42])[C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:22](Br)=[C:21]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:20]=1)([CH3:16])([CH3:15])[CH3:14].C([Cu])#N.[Li+].[Cl-].Br[CH2:49][C:50]([CH3:52])=[CH2:51]>C1COCC1>[C:13]([O:17][C:18](=[O:42])[C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:22]([CH2:51][C:50]([CH3:52])=[CH2:49])=[C:21]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:20]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

9

Reactant 7

HCID 807IodineHCID 3577853-Bromo-2-methyl-1-propeneHCID 433294Lithium ChlorideHCID 10389923tert-Butyl 3,5-bis(benzyloxy)-4-bromobenzoateHCID 178418339ButyllithiumHCID 178418365HCID 178418365, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 595600213,5-Bis-benzyloxy-4-(2-methyl-allyl)-benzoic acid tert-butyl esterYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of Mg pieces (7.9 g, 0.23 mol) in THF (250 mL) was added a catalytic amount of I2, followed by addition of i-PrMgBr (15 mL, 0.16 mol) drop wise. The mixture was heated slowly until refluxed violently. After stirring for 2 hr, the resulting mixture was added to THF (200 mL) and cooled to 0° C. n-BuLi (128 mL, 2.5 M in hexane, 0.32 mol) was added drop wise at 0° C. The mixture was cooled to −78° C. and 3,5-bis-benzyloxy-4-bromo-benzoic acid tert-butyl ester (200c) (50 g, 0.107 mol) was added drop wise. After the mixture was stirred for 1 hr, CuCN (2.85 g, 0.032 mol), LiCl (2.7 g, 0.064 mol), and 3-bromo-2-methyl-propene (43 mL, 0.43 mol) were added sequentially. After stirring for another 30 min at −78° C., TLC (EtOAc/petroleum ether=1/10) showed the reaction was complete. The mixture was quenched with saturated aqueous NH4Cl (150 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated to give the title compound as a yellow oil (40 g, 84.4% yield).

Workup

  1. temperatureThe mixture was heated slowly
  2. temperatureuntil refluxed violently
  3. additionwas added drop wise at 0° C
  4. stirringAfter the mixture was stirred for 1 hr
  5. stirringAfter stirring for another 30 min at −78° C.
  6. customThe mixture was quenched with saturated aqueous NH4Cl (150 mL)
  7. extractionThe aqueous layer was extracted with EtOAc (2×100 mL)
  8. washThe organic layer was washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9e02da337b264b11be08884c9ab8928e
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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