Lithium Hexamethyldisilazide → HCID 68848225, compound

HRID 1723813Notes

Reaction equation

HRID 1723813 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH: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][C:41](OCC)=[O:42]>C1COCC1.CCCC(C)C.CCOCC>[N:33]1[CH:38]=[CH:37][CH:36]=[N:35][C:34]=1[CH2:39][CH2:40][C:41](=[O:42])[CH2:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]([F:22])([F:20])[F:21])=[CH:13][N:12]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3]

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 20213267Ethyl 3-(pyrimidin-2-yl)propanoateHCID 575592331-(Methanesulfonyl)-4-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]piperazine

Product 1

HCID 68848225HCID 68848225, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21882825Ether isohexaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a stirred suspension of 1-(methylsulfonyl)-4-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]piperazine (13.3 g, 39.2 mmol) in THF (200 mL) at −70° C. was added LHMDS (75 mL, 75 mmol) drop wise and the reaction stirred for 20 minutes. A solution of ethyl 3-pyrimidin-2-ylpropanoate (9.2 g, 51 mmol) in THF (55 mL) was then added at −70° 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 (3×250 mL), combined organics were washed with brine (250 mL), dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid. The solid was stirred for 20 minutes in 20% isoHexane/ether (100 mL), filtered and washed with isoHexane and dried to give 4-pyrimidin-2-yl-1-({4-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]piperazin-1-yl}sulfonyl)butan-2-one as an off white solid (15.2 g, 32.2 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 (3×250 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. filtrationfiltered
  10. washwashed with isoHexane
  11. customdried

Sources & evidence

ORD record
ord-d6b83b5cac8e431eaacfeb4ab5e3ed1f
Source dataset
uspto-grants-2009_02
Patent number
US07485644B2

Reaction notes

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