Chloroacetyl chloride → HCID 18442525, compound

HRID 458693Notes

Reaction equation

HRID 458693 reaction equation
[C:1]([O:9][C:10]1[C:15](=[O:16])[NH:14][C:13]([C:17]([C:20](OCC2C=CC=CC=2)=O)([CH3:19])C)=[N:12][C:11]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:35][CH2:36][N:37](C(C)C)C(C)C.ClCC(Cl)=[O:47].C([O-])([O-])=O.[K+].[K+]>CO.CN(C=O)C.[Pd]>[C:1]([O:9][C:10]1[C:15](=[O:16])[N:14]2[CH2:35][C:36](=[O:47])[NH:37][C:17]([CH3:20])([CH3:19])[C:13]2=[N:12][C:11]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 135772689HCID 135772689, compound

Product 1

HCID 18442525HCID 18442525, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Intermediate 29, ethyl 5-(benzoyloxy)-2-(2-(benzyloxycarbonyl)propan-2-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate, (479 mg, 1 mmol) was dissolved in methanol and treated with H2 (1 atm) over 10% Pd/C (106 mg) for 1 hour. The reaction mixture was filtered through Celite and the solvent removed in vacuo. The remaining residue was dissolved in 2 mL of CH2Cl2 to which was added iPr2NEt (0.174 mL, 1 mmol) and chloroacetyl chloride (0.080 mL, 1 mmol). The resulting mixture was allowed to stir for 1 hour, then transferred to a seperatory funnel and washed with 1 N HCl. The organic layer was dried (Na2SO4) and the solvent removed to provide a solid. The solid (1 mmol) was dissolved in 4 mL of DMF. To this was added K2CO3 (140 mg, 1 mmol) and the resulting solution heated to 70° C. After stirring for 2 hours the reaction was quenched with 1 N HCl and transferred to a seperatory funnel. The mixture was washed with ethyl acetate which was then dried over Na2SO4. The solvent was removed in vacuo to provide the title compound as an oil.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. customthe solvent removed in vacuo
  3. dissolutionThe remaining residue was dissolved in 2 mL of CH2Cl2 to which
  4. customtransferred to a seperatory funnel
  5. washwashed with 1 N HCl
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. customthe solvent removed
  8. customto provide a solid
  9. stirringAfter stirring for 2 hours the reaction
  10. customwas quenched with 1 N HCl
  11. customtransferred to a seperatory funnel
  12. washThe mixture was washed with ethyl acetate which
  13. dry with materialwas then dried over Na2SO4
  14. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-b698b607e56b435f8519bc283c69497d
Source dataset
uspto-grants-2007_03
Patent number
US07192948B2

Reaction notes

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