Allyl bromide → Di-tert-butyl (2S,4S)-2-Allyl-4-(Boc-amino)pentanedioate

HRID 591286Notes

Reaction equation

HRID 591286 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:36](Br)[CH:37]=[CH2:38]>O1CCCC1>[CH2:38]([C@H:11]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:10][C@@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:37]=[CH2:36]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 86647571Di-tert-butyl Boc-L-glutamate

Product 1

HCID 58185190Di-tert-butyl (2S,4S)-2-Allyl-4-(Boc-amino)pentanedioate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 719 mg (2.00 mmol) di-tert-butyl N-(tert-butoxycarbonyl)-L-glutamate in tetrahydrofuran (12 mL) at −78° C., lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1.0 M in tetrahydrofuran, 4.40 mL) was added dropwise. The solution was stirred for 30 min, then allyl bromide (0.52 mL, 6.00 mmol) was added dropwise. The reaction was stirred at −78° C. overnight and then quenched at −10° C. by the addition of 10 mL of 2 N aqueous hydrogen chloride. The mixture was warmed to room temperature poured into 10 mL 1 N aqueous hydrogen chloride and extracted with dichloromethane (3×30 mL). The organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was purified on silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated.

Workup

  1. stirringThe reaction was stirred at −78° C. overnight
  2. customquenched at −10° C. by the addition of 10 mL of 2 N aqueous hydrogen chloride
  3. additionpoured into 10 mL 1 N aqueous hydrogen chloride
  4. extractionextracted with dichloromethane (3×30 mL)
  5. dry with materialThe organic phases were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified on silica gel using a hexane/ethyl acetate gradient
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-27bfcaf7afb248c698e30b778e061ca9
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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