Acetone → 2-(2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-3-methylpentanoic acid

HRID 883539Notes

Reaction equation

HRID 883539 reaction equation
[C:1](Br)(=[O:10])[C:2]1[NH:9][C:7](=[O:8])[NH:6][C:4](=[O:5])[CH:3]=1.[NH2:12][C@H:13]([C:18]([OH:20])=[O:19])[C@H:14]([CH2:16][CH3:17])[CH3:15].C(=O)=O.CC(C)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[O:8]=[C:7]1[NH:9][C:2]([C:1]([NH:12][CH:13]([CH:14]([CH3:15])[CH2:16][CH3:17])[C:18]([OH:20])=[O:19])=[O:10])=[CH:3][C:4](=[O:5])[NH:6]1

Participants

7

Reactant 4

HCID 180AcetoneHCID 280Carbon DioxideHCID 6306L-IsoleucineHCID 461847302,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carbonyl bromide4×

Product 1

HCID 246931482-(2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-3-methylpentanoic acid

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

In a dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, a thermometer, a nitrogen inlet tube and the dropping funnel containing the orotoyl bromide solution, 9.84 g (75 mmol) of Isoleucine is suspended, with stirring, in 100 mL of dry DCM. To this suspension a catalytic amount (˜0.1 mmol) of DMAP is also added. The suspension is stirred in a dry ice and acetone bath to a temperature of about −15° C. When the target temperature is reached the drop wise addition of orotoyl bromide is commenced. Addition of orotoyl bromide continues, with constant cooling and stirring, until all of the orotoyl bromide is added, after which the reaction is allowed to warm to room temperature with constant agitation. The solution is then filtered to remove any remaining Isoleucine and the volatile DCM is removed from the filtrate under reduced pressure, the remainder is then purified by flash chromatography (ethyl acetate/hexanes; 1/5), yielding 2-(2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-3-methylpentanoic acid.

Workup

  1. customIn a dry 3-necked, round bottomed flask, equipped with a magnetic stirrer
  2. temperaturewith constant cooling
  3. filtrationThe solution is then filtered
  4. customto remove any remaining Isoleucine
  5. customthe volatile DCM is removed from the filtrate under reduced pressure
  6. customthe remainder is then purified by flash chromatography (ethyl acetate/hexanes; 1/5)

Sources & evidence

ORD record
ord-d9185d211bc1473daf9d7d3d792488d8
Source dataset
uspto-grants-2012_08
Patent number
US08236952B2

Reaction notes

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