Potassium Carbonate → Methyl(2Z)-2-bromo-4-[N-(tert-butoxycarbonyl)amino]-5-methylhexenoate

HRID 424975Notes

Reaction equation

HRID 424975 reaction equation
[Br:1]N1C(=O)CCC1=O.C(=O)([O-])[O-].[K+].[K+].[CH3:15][O:16][C:17]([CH:19]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:18].[C:39]([O:43][C:44]([NH:46][C@H:47]([CH:51]=O)[CH:48]([CH3:50])[CH3:49])=[O:45])([CH3:42])([CH3:41])[CH3:40]>ClCCl>[Br:1]/[C:19](=[CH:51]\[CH:47]([NH:46][C:44]([O:43][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:45])[CH:48]([CH3:49])[CH3:50])/[C:17]([O:16][CH3:15])=[O:18]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 17453Acetic acid, 2-(triphenylphosphoranylidene)-, methyl esterHCID 67184N-bromobutanimideHCID 6917569(S)-tert-Butyl (3-methyl-1-oxobutan-2-yl)carbamate

Product 1

HCID 59841266Methyl(2Z)-2-bromo-4-[N-(tert-butoxycarbonyl)amino]-5-methylhexenoateYield 8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

N-Bromosuccinimide (4.60 g, 25.9 mmol) and anhydrous potassium carbonate (8.10 g, 58.8 mmol) are successively added, over a period of 20 minutes, to a solution of (methoxycarbonylmethylene)triphenylphosphorane (PH3P═CH—CO2Me, 7.90 g, 23.5 mmol) in dichloromethane (60 ml) cooled to −20.0° C. The mixture, yellow-brown, is left under stirring for 20 min and freshly prepared N-(Boc)Valinal 2 (4.74 g, 23.5 mmol) dissolved in CH2Cl2 (20 ml) is instilled. The addition completed, the mixture is left for 30 min at −20.0° C. and for 1 h at ambient temperature. A TLC check indicates the total disappearance of the aldehyde. The mixture is filtered on a fritted disc coated with celite, and the fritted disc is rinsed with ether. After evaporation of the filtrate under a vacuum, the yellow oil obtained is chromatographed on a silica gel (elution gradient Heptane/AcOEt 90/10→75/25). 2.10 g (27%, Rf=0.46 (AcOEt/Hept 1/3)) of pure isomer E, 0.63 g of mixture (7%, Z+E) and 3.2 g (41%, Rf=0.35 (AcOEt/Hept 1/3)) of pure isomer Z are obtained.

Workup

  1. waitThe mixture, yellow-brown, is left
  2. additionThe addition
  3. waitthe mixture is left for 30 min at −20.0° C. and for 1 h at ambient temperature
  4. filtrationThe mixture is filtered on a fritted disc
  5. washthe fritted disc is rinsed with ether
  6. customAfter evaporation of the filtrate under a vacuum
  7. customthe yellow oil obtained
  8. customis chromatographed on a silica gel (elution gradient Heptane/AcOEt 90/10→75/25)

Sources & evidence

ORD record
ord-f84381683deb418bb9021f5a7e3e11c7
Source dataset
uspto-grants-2012_01
Patent number
US08106089B2

Reaction notes

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