Chloride → 5-Ethyl-1-(3-acetoxypropyloxymethyl)-6-(3,5-dimethylbenzyl)uracil

HRID 1072968

Reaction equation

HRID 1072968 reaction equation
[CH2:1]([C:3]1[C:4](=[O:19])[NH:5][C:6](=[O:18])[NH:7][C:8]=1[CH2:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[CH:11]=1)[CH3:2].CC1C=C(C=C(C)C=1)CC1NC(=O)NC(=O)C=1C(C)C.BrC(C(C)C)C(O)=O.BrC(CC)C(O)=O.[C:55]([O:58][CH2:59][CH2:60][CH2:61][O:62][CH2:63]OC(=O)C)(=[O:57])[CH3:56].C[Si](C)(C)N[Si](C)(C)C.Cl[Si](C)(C)C.[Cl-].[Na]>C(#N)C.ClCCl>[CH2:1]([C:3]1[C:4](=[O:19])[NH:5][C:6](=[O:18])[N:7]([CH2:63][O:62][CH2:61][CH2:60][CH2:59][O:58][C:55](=[O:57])[CH3:56])[C:8]=1[CH2:9][C:10]1[CH:11]=[C:12]([CH3:17])[CH:13]=[C:14]([CH3:16])[CH:15]=1)[CH3:2]

Participants

12

Reactant 9

HCID 312ChlorideHCID 6397ChlorotrimethylsilaneHCID 66552-Bromobutanoic acidHCID 112682-Bromoisovaleric acidHCID 13838HexamethyldisilazaneHCID 5360545SodiumHCID 106826455-Ethyl-6-(3,5-dimethylbenzyl)uracilHCID 107309016-(3,5-Dimethylbenzyl)-5-isopropyluracilHCID 124808481-Acetoxy-3-acetoxymethoxypropane

Product 1

HCID 223866115-Ethyl-1-(3-acetoxypropyloxymethyl)-6-(3,5-dimethylbenzyl)uracilYield 87%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a suspension of 5-ethyl-6-(3,5-dimethylbenzyl)uracil (645 mg, 5 mmol) (prepared as described for the preparation of 6-(3,5-dimethylbenzyl)-5-isopropyluracil in the above Example 1-A but in replacing the 2-bromo-3-methylbutanoic acid by the 2-bromobutanoic acid) and 1-acetoxy-3-acetoxymethoxypropane (prepared as described in the above Example 1-B) (950 mg, 5 mmol) in ethanenitrile (25 ml), were added hexamethyldisilazane (810 mg, 5 mmol) and chlorotrimethylsilane (545 mg, 5 mmol). After 10 minutes under stirring at 20° C., it was added dropwise thereto, in 10 minutes, a solution of tinIV chloride (782 mg, 2.4 mmol) in ethanenitrile (7 ml). After 14 h under stirring, it was added to the reaction medium dichloromethane (70 ml) and an aqueous saturated sodium hydrogenocarbonate solution (70 ml). The organic phase was separated by decantation and the aqueous phase was extracted with dichloromethane (3×50 ml). The collected organic phases were washed with saturated sodium hydrogenocarbonate solution (25 ml), with water (25 ml) and with an aqueous saturated sodium chloride solution (25 ml). The organic phase was dried over sodium sulfate, concentrated, and subjected to a flash column chromatography on silica gel (ethyl acetate/petroleum ether 1:1) to give 0.85 g (87%) of 5-ethyl-1-(3-acetoxypropyloxymethyl)-6-(3,5-dimethylbenzyl)uracil.

Workup

  1. customprepared
  2. customprepared
  3. additionit was added dropwise
  4. waitin 10 minutes
  5. stirringAfter 14 h under stirring
  6. customThe organic phase was separated by decantation
  7. extractionthe aqueous phase was extracted with dichloromethane (3×50 ml)
  8. washThe collected organic phases were washed with saturated sodium hydrogenocarbonate solution (25 ml), with water (25 ml) and with an aqueous saturated sodium chloride solution (25 ml)
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-acc159f6cf094af0b1ef62a16ff553a4
Source dataset
uspto-grants-2005_06
Patent number
US06911450B1

Linked notes

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