Hydrochloric Acid → 6-chloro-1-(cyclobutylmethyl)-3-methylpyrimidine-2,4(1H,3H)-dione

HRID 900702Notes

Reaction equation

HRID 900702 reaction equation
ClCC1N[C:7](=O)[NH:6][C:5](=[O:10])C=1.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1P(C1C=CC=CC=1)C1C=CC=CC=1.[CH:30]1([CH2:34][OH:35])CC[CH2:31]1.[ClH:36]>C1COCC1.O1CCOCC1.O1CCOCC1>[Cl:36][C:31]1[N:11]([CH2:16][CH:15]2[CH2:12][CH2:13][CH2:14]2)[C:5](=[O:10])[N:6]([CH3:7])[C:34](=[O:35])[CH:30]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 732736-(Chloromethyl)-2,4(1H,3H)-pyrimidinedioneHCID 78130CyclobutylcarbinolHCID 6218932-Pyridyldiphenylphosphine

Product 1

HCID 223496026-chloro-1-(cyclobutylmethyl)-3-methylpyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 22018518Dioxane tetrahydrofuranSolvent

Procedure

To 2 cooled (0° C.) slurry of 6-chloromethyluracil (2.0 g, 12 mmol) in THF/dioxan (1:1, 16 ml) is added 2-pyridyldiphenylphosphine (3.60 g, 13.7 mmol) and cyclobutanemethanol (1.3 ml, 13.8 mmol), followed by di-t-butylazodicarboxylate (3.15 g, 13.7 mmol). The reaction is stirred overnight at ambient temperature, treated with 4M HCl in dioxan (15 ml) and evaporated. The residue is taken up in dichloromethane, washed with 3.5M HCl, dried over magnesium sulfate and evaporated. The crude product is purified by flash chromatography (100:1 dichloromethanemethanol elution) to afford 6-chloro-1-cyclobutylmethyl-3-methyl-1H-pyrimidine-2,4-dione, 1H NMR (400 MHz, CDCl3) δ 1.70-2.0 (m 6H), 2.60 (m 1H), 3.20 (s 3H), 4.00 (d J 7 2H), 5.78 (s 1H), which is dissolved in n-butanol (50 ml). Veratrylamine (4 ml, 26.5 mmol) is added and the reaction heated to reflux for 16 hours.

Workup

  1. customevaporated
  2. washwashed with 3.5M HCl
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe crude product is purified by flash chromatography (100:1 dichloromethanemethanol elution)

Sources & evidence

ORD record
ord-50b2219b40df44308a4eaab12134e046
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

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