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tert-Butyl bromoacetate → 1-[(tert-Butoxycarbonyl)methyl]-Nalpha-benzyloxycarbonyl-D-tryptophan

HRID 1108206
Notes
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Reaction equation

HRID 1108206 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([O:18][C:19]([NH:21][C@@H:22]([C:33]([OH:35])=[O:34])[CH2:23][C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[NH:26][CH:25]=1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Br[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>O1CCCC1>[C:41]([O:40][C:38]([CH2:37][N:26]1[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24]([CH2:23][C@H:22]([C:33]([OH:35])=[O:34])[NH:21][C:19]([O:18][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:20])=[CH:25]1)=[O:39])([CH3:44])([CH3:43])[CH3:42]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 700663N-(Benzyloxycarbonyl)-D-tryptophanHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 538032101-[(tert-Butoxycarbonyl)methyl]-Nalpha-benzyloxycarbonyl-D-tryptophanYield 101.7%

Reagents, catalysts & solvents 1

HCID 8028Tetrahydrofuran
Solvent
3×

Procedure

600 ml of a solution of NaHMDS (sodium salt of 1,1,1,3,3,3-hexamethyldisilazane) (1M) in tetrahydrofuran are added dropwise, at -78° C. under an inert atmosphere, to a solution of 100 g of Nα-benzyloxycarbonyl-D-tryptophan in a liter of anhydrous tetrahydrofuran. After one hour, the temperature is brought to 0° C. and a solution of 64 g of tert-butyl bromoacetate in 50 ml of anhydrous tetrahydrofuran is added dropwise. The reaction mixture is then brought to ambient temperature and the solvent is subsequently evaporated off in vacuo. The residue is diluted with dichloromethane and the solution is acidified by adding an aqueous 4N hydrochloric acid solution. After extraction with dichloromethane, the organic phases are dried over sodium sulphate and then concentrated in vacuo. 136 g of the expected product are obtained.

Workup

  1. customis brought to 0° C.
  2. customis then brought to ambient temperature
  3. customthe solvent is subsequently evaporated off in vacuo
  4. additionThe residue is diluted with dichloromethane
  5. additionby adding an aqueous 4N hydrochloric acid solution
  6. extractionAfter extraction with dichloromethane
  7. dry with materialthe organic phases are dried over sodium sulphate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-858fd614e1bd497186f9d18efd6ddb17
Source dataset
uspto-grants-2000_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06066633

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes