4-Nitrobenzyl bromide → Di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-(4-nitrobenzyl)-L-glutamate

HRID 591259Notes

Reaction equation

HRID 591259 reaction equation
[C:1]([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:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[N+:36]([C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][CH:40]=1)([O-:38])=[O:37]>O1CCCC1>[C:4]([O:3][C:1]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][C@H:11]([CH2:43][C:42]1[CH:45]=[CH:46][C:39]([N+:36]([O-:38])=[O:37])=[CH:40][CH:41]=1)[C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 660114-Nitrobenzyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 86647571Di-tert-butyl Boc-L-glutamate

Product 1

HCID 89136291Di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-(4-nitrobenzyl)-L-glutamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

5.0 g (13.9 mmol) of di-tert-butyl Boc-glutamate (Journal of Peptide Research (2001), 58, 338) were dissolved in 30 mL of tetrahydrofuran and cooled to −70° C. 30.6 mL (30.6 mmol) of a 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran were added dropwise over a period of 85 min at this temperature and the mixture was stirred at −70° C. for another 2 hours. 9.0 g (41.7 mmol) of 4-nitrobenzyl bromide in 30 mL of tetrahydrofuran were than added dropwise, and after 1.5 h at this temperature, the cooling bath was removed and 100 mL of 2N aqueous hydrochloric acid and 450 mL of dichloromethane were added. The organic phase was separated off, washed with water (3×150 mL), dried over sodium sulfate and filtered, and the filtrate was concentrated. The crude product obtained in this manner was chromatographed on silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated.

Workup

  1. additionthan added dropwise
  2. waitafter 1.5 h at this temperature
  3. customthe cooling bath was removed
  4. addition100 mL of 2N aqueous hydrochloric acid and 450 mL of dichloromethane were added
  5. customThe organic phase was separated off
  6. washwashed with water (3×150 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-3bd73b695cb94dad835043409046dc3c
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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