Lithium Hexamethyldisilazide → HCID 68848147, compound

HRID 1723804Notes

Reaction equation

HRID 1723804 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[CH:13][N:12]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[N:33]1[CH:38]=[CH:37][CH:36]=[N:35][C:34]=1[CH2:39][CH2:40][CH2:41][C:42](OCC)=[O:43]>C1COCC1>[N:33]1[CH:38]=[CH:37][CH:36]=[N:35][C:34]=1[CH2:39][CH2:40][CH2:41][C:42](=[O:43])[CH2:1][S:2]([N:5]1[CH2:6][CH2:7][N:8]([C:11]2[N:12]=[CH:13][C:14]([O:17][CH2:18][C:19]([F:22])([F:20])[F:21])=[CH:15][N:16]=2)[CH2:9][CH2:10]1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 10058457Ethyl 4-(pyrimidin-2-yl)butanoateHCID 575592412-[4-(Methanesulfonyl)piperazin-1-yl]-5-(2,2,2-trifluoroethoxy)pyrimidine

Product 1

HCID 68848147HCID 68848147, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a stirred suspension of 2-[4-(methylsulfonyl)piperazin-1-yl]-5-(2,2,2-trifluoroethoxy)pyrimidine (8.05 g, 23.6 mmol) in THF (175 mL) at −78° C. was added LHMDS (47.2 mL, 47.2 mmol) dropwise and the reaction stirred for 15 minutes. A solution of ethyl 4-pyrimidin-2-ylbutanoate (5.5 g, 28.3 mmol) in THF (50 mL) was then added at −78° C., warmed to −20° C. and stirred for 2 hours. The reaction was then quenched by addition of a saturated solution of NH4Cl (250 mL), extracted twice with EtOAc (2×250 mL), combined organics were washed with brine (250 mL), dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid. This was then purified by flash chromatography (silica gel, 50% EtOAc/hexanes) to give 5-pyrimidin-2-yl-1-({4-[5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]piperazin-1-yl}sulfonyl)pentan-2-one as an off white solid (9.47 g, 19.4 mmol, 82%).

Workup

  1. stirringstirred for 2 hours
  2. customThe reaction was then quenched by addition of a saturated solution of NH4Cl (250 mL)
  3. extractionextracted twice with EtOAc (2×250 mL)
  4. washcombined organics were washed with brine (250 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a yellow solid
  9. customThis was then purified by flash chromatography (silica gel, 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d5568b570a72481bbbf435214bf59efd
Source dataset
uspto-grants-2009_02
Patent number
US07485644B2

Reaction notes

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