(5S)-2-(tert-Butoxycarbonyl)-5-[(tert-butoxycarbonyl)amino]-2-(4-hydroxybenzyl)hexanedioic acid 6-tert-butyl ester → Di-tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-5-(4-hydroxybenzyl)hexanedioate

HRID 591275Notes

Reaction equation

HRID 591275 reaction equation
[C:1]([O:5][C:6](=[O:37])[C@@H:7]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:8][CH2:9][C:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)C(O)=O)([CH3:4])([CH3:3])[CH3:2]>O1CCCC1>[C:33]([O:32][C:30]([NH:29][C@@H:7]([CH2:8][CH2:9][CH:10]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([OH:21])=[CH:19][CH:20]=1)[C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:37])=[O:31])([CH3:34])([CH3:35])[CH3:36]

Participants

3

Reactant 1

HCID 70941175(5S)-2-(tert-Butoxycarbonyl)-5-[(tert-butoxycarbonyl)amino]-2-(4-hydroxybenzyl)hexanedioic acid 6-tert-butyl ester

Product 1

HCID 70957101Di-tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-5-(4-hydroxybenzyl)hexanedioateYield 88.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 730 mg (5S)-2-(tert-butoxycarbonyl)-5-[(tert-butoxycarbonyl)amino]-2-(4-hydroxybenzyl)hexanedioic acid 6-tert-butyl ester (1.39 mmol) and 290 mg 4-N,N-dimethylaminopyridine (2.37 mmol) in tetrahydrofuran (10 mL) was heated under reflux for 18 hours. Since the turnover was only approx. 75% then, and to drive the reaction to completion, the mixture was evaporated, the residue dissolved in 1,4-dioxane, and heated under reflux for another 2 hours after which turnover was complete. The mixture was evaporated and the residue was purified by column chromatography on silica gel (2.5→35% ethyl acetate in hexane), to give 590 mg (88% yield) of the target compound featuring an HNMR spectrum in line with the HNMR data for example 12d.

Workup

  1. temperatureunder reflux for 18 hours
  2. customthe reaction to completion
  3. customthe mixture was evaporated
  4. dissolutionthe residue dissolved in 1,4-dioxane
  5. temperatureheated
  6. temperatureunder reflux for another 2 hours after which turnover
  7. customThe mixture was evaporated
  8. customthe residue was purified by column chromatography on silica gel (2.5→35% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-180a55eeab6b43c492695784296d7008
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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