Hydrochloric Acid → Uracel, 3-ethyl-

HRID 377182Notes

Reaction equation

HRID 377182 reaction equation
N[C:2]1[N:7]([CH2:8][C:9]2C=CC(Cl)=CC=2)[C:6](=[O:16])[NH:5][C:4](=O)[C:3]=1NC(=O)C(C)C.CC(C)([O-:27])C.[K+].C(Br)C.Cl>CN(C=O)C>[CH2:8]([N:7]1[C:2](=[O:27])[CH:3]=[CH:4][NH:5][C:6]1=[O:16])[CH3:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6332Ethyl Bromide3×HCID 21715768HCID 21715768, compoundHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 165291Uracel, 3-ethyl-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

13.47 g (40 mM) of 6-amino-1-(4-chlorobenzyl)-5-isobutyrylaminouracil were dissolved in 130 ml of DMF, treated at 5° C. with 4.57 g (40.8 mM) potassium t-butoxide and after dissolution, 3.28 ml (44 mM) of ethyl bromide added. After 3 hours, another 1.14 g of t-BuOK and 1.64 ml of ethyl bromide were added. After a further 1.5 hours, 1.64 ml of ethyl bromide was supplemented. After a total of 22 hours, the solution was neutralized with 1N HCl to pH 7 and the solvents evaporated in vacuo. The residue was taken up in dichloromethane-water and the organic phase collected giving 17.66 of crude 3-ethyl uracil, which was dissolved in 17.6 ml of 1N NaOH and heated under reflux for 1 hour. The solution was treated twice with 1 g of charcoal, filtered and neutralized with 5N HCl to pH 7. The solid was diluted with water, collected, and dried. The crude material was recrystallized from methanol to give 7.42 g (49.2%) of 3-(4-chlorobenzyl)-1-ethyl-8-isopropyl-xanthine, mp 221-2° C.

Workup

  1. additionadded
  2. waitAfter a further 1.5 hours
  3. customAfter a total of 22 hours
  4. customthe solvents evaporated in vacuo
  5. customthe organic phase collected

Sources & evidence

ORD record
ord-1a7be56821b34ec68ec252cebcfd7075
Source dataset
uspto-grants-2000_02
Patent number
US06025361

Reaction notes

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