Tetrahydrofuran → Methyl 4,4-dimethyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate

HRID 1399721Notes

Reaction equation

HRID 1399721 reaction equation
[CH3:1][C:2]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:6]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[N:5]=[C:4]([N:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1COCC1.I[CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44]>CN(P(N(C)C)(N(C)C)=O)C.CN(C=O)C>[CH3:42][C:43]([CH3:46])([CH3:45])[CH2:44][CH:8]([C:7]1[C:2]([CH3:1])=[N:3][C:4]([N:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)=[N:5][C:6]=1[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)[C:9]([O:11][CH3:12])=[O:10]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 3251421Potassium bis(trimethylsilyl)amideHCID 66955539Methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetate

Product 1

HCID 50994998Methyl 4,4-dimethyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoateYield 9.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-15 °C

Procedure

To a cooled (−15° C.) solution of methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetate (0.200 g; 0.589 mmol) in a mixture of dry DMF (1.2 mL) and HMPA (0.3 mL) was wadded a 1N solution of KHMDS in THF (0.825 mL; 0.825 mmol) dropwise and the mixture was stirred at (−15° C.) for 15 min, followed by the dropwise addition of 1-iodo-2,2-dimethylpropane (0.313 mL; 2.357 mmol). After stirring for 1 h at (−15° C.) the mixture was allowed to warm up to room temperature and stirring was carried on 4 h. The reaction was quenched by adding a saturated solution of ammonium chloride and the mixture was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane furnished 0.024 g (9%) of the title compound.

Workup

  1. stirringAfter stirring for 1 h at (−15° C.) the mixture
  2. temperatureto warm up to room temperature
  3. stirringstirring
  4. waitwas carried on 4 h
  5. customThe reaction was quenched
  6. additionby adding a saturated solution of ammonium chloride
  7. extractionthe mixture was extracted twice with ethyl acetate
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane

Sources & evidence

ORD record
ord-724e6a4e0a4841ae977d870661cb6879
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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