Ammonium Chloride → HCID 69809502, compound

HRID 2088448Notes

Reaction equation

HRID 2088448 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[NH:8][C:9](=[O:12])[NH:10][CH:11]=1)=[O:5])[CH3:2].[CH3:20][Si](C)(C)[N-][Si](C)(C)C.[Li+].C[Si](C)(C)[CH2:32][CH2:33][O:34][CH2:35]Cl.[NH4+].[Cl-]>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)[NH:8][C:9](=[O:12])[N:10]([CH2:35][O:34][CH2:33][CH2:32][CH3:20])[CH:11]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 2733832Lithium HexamethyldisilazideHCID 66955131HCID 66955131, compound

Product 1

HCID 69809502HCID 69809502, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-fluoro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (205 mg, 0.78 mmol) in THF (3 mL) was added lithium hexamethyldisilazide (LiHMDS, 0.78 mL of 1M THF solution, 0.78 mmol) at 0° C. under argon atmosphere. The reaction mixture was stirred for 10 minutes, and then 2-trimethylsilylethyoxymethyl chloride (SEMCl, 0.137 mL, 0.78 mmol) was added dropwise at 0° C. The mixture was allowed to reach rt and was stirred overnight. Saturated aqueous NH4Cl was added and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried under Na2SO4, filtered and concentrated to dryness under reduced pressure. Purification of the residue by flash column (hexane/ethyl acetate gradient) gave 4-(4-fluoro-phenyl)-2-oxo-1-propoxymethyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (155 mg, 51%).

Workup

  1. customto reach rt
  2. stirringwas stirred overnight
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. customdried under Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customPurification of the residue by flash column (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-39dbfc74a6184e96afc035868f9f5295
Source dataset
uspto-grants-2013_05
Patent number
US08435990B2

Reaction notes

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