4,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide → 1-[4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]-6-trimethylsilyl-5-hexyn-1-one

HRID 2082033Notes

Reaction equation

HRID 2082033 reaction equation
[CH3:1][C:2]([C:5]1[C:10]([OH:11])=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[N:8]=[C:7]([C:16](N(OC)C)=[O:17])[N:6]=1)([CH3:4])[CH3:3].[CH3:22][Si:23]([CH3:32])([CH3:31])[C:24]#[C:25][CH2:26][CH2:27][CH2:28][Mg]Br>O1CCCC1>[CH3:15][C:12]([C:9]1[C:10]([OH:11])=[C:5]([C:2]([CH3:3])([CH3:1])[CH3:4])[N:6]=[C:7]([C:16](=[O:17])[CH2:28][CH2:27][CH2:26][C:25]#[C:24][Si:23]([CH3:32])([CH3:31])[CH3:22])[N:8]=1)([CH3:13])[CH3:14]

Participants

4

Reactant 2

HCID 100401704,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamideHCID 178504199HCID 178504199, compound

Product 1

HCID 104520651-[4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]-6-trimethylsilyl-5-hexyn-1-oneYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide (1,00 g, 3.38 mmols) in tetrahydrofuran (50 mL) under nitrogen atmosphere is added a freshly prepared 0.105M solution of 5-trimethylsilylpent-4-ynyl magnesium bromide (81 mL, 8.5 mmols) [from 5-bromo-1-trimethylsilyl-1pentyne (3.86 g, 17.5 mmol) and magnesium (1.50 g, 61.7 mg-atom) in tetrahydrofuran (140 mL)] dropwise. After stirring 16 hours, the resulting mixture is quenched with saturated aqueous ammonium chloride solution and extracted with ethyl ether. The combined extracts are washed with brine and the organic phase is dried over magnesium sulfate. Concentration under vacuum is followed by purification of the organic residue by flash chromatography (SiO2, 20% ethyl acetate/hexane) to give 0.97 g (77%) of the title compound which is used without further purification to make the compound of Example 7.

Workup

  1. customthe resulting mixture is quenched with saturated aqueous ammonium chloride solution
  2. extractionextracted with ethyl ether
  3. washThe combined extracts are washed with brine
  4. dry with materialthe organic phase is dried over magnesium sulfate
  5. concentrationConcentration under vacuum
  6. customis followed by purification of the organic residue by flash chromatography (SiO2, 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e6552dc7ec2d471d8e3285bc67fc7e63
Source dataset
uspto-grants-1993_02
Patent number
US05187175

Reaction notes

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