Methyl iodide → 4-[5-(Propane-2-sulfonyl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1352331Notes

Reaction equation

HRID 1352331 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:15][C:16]([S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][Si]([NH-])(C)C.C[Si]([NH-])(C)C.[K+].[K+].IC.C(OCC)(=O)C.CCCCCCC>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:15][C:16]([S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 21899848Ethylacetate heptaneHCID 684069054-(5-Ethanesulfonyl-thiazol-2-yl)-piperazine-1-carboxylic acid tert-butyl esterHCID 86591204Potassium bis(trimethylsilylamide)

Product 1

HCID 684062884-[5-(Propane-2-sulfonyl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.83 mmol 4-(5-ethanesulfonyl-thiazol-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (Example 32(b)) in 3 ml tetrahydrofuran at −78° C. was added dropwise 1.08 mmol potassium bis(trimethylsilylamide) solution (0.91 M in tetrahydrofuran). After 3 min, a solution of 1.24 mmol iodomethane in 2 ml tetrahydrofuran was added dropwise and stirring continued for 10 min at −78° C. The reaction mixture was then allowed to warm to room temperature and poured onto tetrahydrofuran/ethyl acetate (1:1). The mixture was washed with brine and the organic phase was dried over sodium sulphate and concentrated in vacuo. Chromatography (SiO2, ethyl acetate/heptane) afforded the title compound as a white crystalline solid (yield 30%). MS (m/e): 376.1 (M+H+, 100%).

Workup

  1. waitcontinued for 10 min at −78° C
  2. additionpoured onto tetrahydrofuran/ethyl acetate (1:1)
  3. washThe mixture was washed with brine
  4. dry with materialthe organic phase was dried over sodium sulphate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4958b00820dd4717947378b820d3104c
Source dataset
uspto-grants-2007_05
Patent number
US07220744B2

Reaction notes

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