Sodium hydride → 2,3-dibenzyl 3-tert-butyl 1-cyclopropyl-4-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)-2(R),3(R,S),3-butanetricarboxylate

HRID 1108327Notes

Reaction equation

HRID 1108327 reaction equation
[CH:1]1([CH2:4][C@@H:5]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH:6]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:37][N:38]1[C:42](=[O:43])[C:41]([CH3:45])([CH3:44])[N:40]([CH3:46])[C:39]1=[O:47]>COCCOC>[CH:1]1([CH2:4][C@@H:5]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[C:6]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])([C:7]([O:9][CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:8])[CH2:37][N:38]2[C:42](=[O:43])[C:41]([CH3:44])([CH3:45])[N:40]([CH3:46])[C:39]2=[O:47])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109334353-Bromomethyl-1,5,5-trimethylhydantoinHCID 1317218122,3-dibenzyl 3-tert-butyl 1-cyclopropyl-2(R),3(R,S),3-propane-tricarboxylate

Product 1

HCID 1317218132,3-dibenzyl 3-tert-butyl 1-cyclopropyl-4-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)-2(R),3(R,S),3-butanetricarboxylateYield 74.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A solution of 6.4 g of 2,3-dibenzyl 3-tert-butyl 1-cyclopropyl-2(R),3(R,S),3-propanetricarboxylate (1:1 mixture of diastereoisomers) in 30 ml of 1,2-dimethoxyethane was treated with 0.446 g of an 80% dispersion of sodium hydride in mineral oil. The mixture was stirred at room temperature for 30 minutes. A solution of 3.84 g of 1-(bromomethyl)-3,4,4-trimethyl-2,5-imidazolinedione in 20 ml of 1,2-dimethoxyethane was added dropwise over 15 minutes. The mixture was stirred at room temperature for 36 hours, the solvent was evaporated and the residue was dissolved in ethyl acetate and washed with water and saturated sodium chloride solution. After drying over anhydrous magnesium sulphate the solvent was evaporated. The residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (7:3) and subsequently hexane/ethyl acetate (6:4) for the elution to give 6.4 g of 2,3-dibenzyl 3-tert-butyl 1-cyclopropyl-4-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)-2(R),3(R,S),3-butanetricarboxylate as a 1:1 mixture of diastereoisomers in the form of a clear oil.

Workup

  1. stirringThe mixture was stirred at room temperature for 36 hours
  2. customthe solvent was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with water and saturated sodium chloride solution
  5. dry with materialAfter drying over anhydrous magnesium sulphate the solvent
  6. customwas evaporated
  7. customThe residue was purified by flash chromatography on silica gel
  8. washfor the elution

Sources & evidence

ORD record
ord-b603908bc90e4f77b758f22c273f38cd
Source dataset
uspto-grants-2000_05
Patent number
US06066662

Reaction notes

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