Tetrahydrofuran → Methyl 4-methoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)butanoate

HRID 1399690Notes

Reaction equation

HRID 1399690 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.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1[CH2:40][O:39][CH2:38][CH2:37]1.COCCBr>CN(C=O)C>[CH3:40][O:39][CH2:38][CH2:37][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

6

Reactant 4

HCID 8028TetrahydrofuranHCID 809722-Bromoethyl methyl etherHCID 2733832Lithium HexamethyldisilazideHCID 66955539Methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetate

Product 1

HCID 50997143Methyl 4-methoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)butanoateYield 15.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (0.100 g; 0.295 mmol) in dry DMF (1.5 mL) was wadded a 1N solution of LHMDS in THF (0.324 mL; 0.324 mmol) dropwise and the mixture was stirred at (−15° C.) for 15 min, followed by the dropwise addition of 2-bromoethyl methyl ether (0.083 mL; 0.884 mmol). After stirring for 2 h at (−15° C.) the mixture was allowed to warm up to room temperature. After 1 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 0.018 g (15%) of the title compound as a colorless oil.

Workup

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

Sources & evidence

ORD record
ord-c2201ad7cd1d4ecb88b57de1b831ddb8
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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