Lithium Hexamethyldisilazide → Di-tert-butyl (4S)-4-{4-[3-(benzyloxy)propyl]benzyl}-N-(tert-butoxycarbonyl)-L-glutamate

HRID 591266Notes

Reaction equation

HRID 591266 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]([O:43][CH2:44][CH2:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53]Br)=[CH:49][CH:48]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>O1CCCC1>[CH2:36]([O:43][CH2:44][CH2:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][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:49][CH:48]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 86647571Di-tert-butyl Boc-L-glutamateHCID 89120206HCID 89120206, compound

Product 1

HCID 131734509Di-tert-butyl (4S)-4-{4-[3-(benzyloxy)propyl]benzyl}-N-(tert-butoxycarbonyl)-L-glutamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.08 g (3.38 mmol) di-tert-butyl N-(tert-butoxycarbonyl)-L-glutamate in tetrahydrofuran (18 mL) at −78° C., lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1.0 M in tetrahydrofuran, 6.20 mL) was added dropwise. The solution was stirred for 2 h, then 1-[3-(benzyloxy)propyl]-4-(bromomethyl)benzene (1.01 g, 2.82 mmol) dissolved in 5 mL tetrahydrofuran were added slowly. The reaction was stirred for additional 2 h and then quenched 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. additionwere added slowly
  2. stirringThe reaction was stirred for additional 2 h
  3. customquenched by the addition of 10 mL of 2 N aqueous hydrogen chloride
  4. additionpoured into 10 mL 1 N aqueous hydrogen chloride
  5. extractionextracted with dichloromethane (3×30 mL)
  6. dry with materialThe organic phases were dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified on silica gel using a hexane/ethyl acetate gradient
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-0d880c5436e844349ef1d01fa1f01605
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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