Lithium diisopropylamide → 3-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]propionic acid ethyl ester

HRID 2353337

Reaction equation

HRID 2353337 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH3:2].[Li+].CC([N-]C(C)C)C.I[CH2:32][CH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>C1COCC1.COC1SC(=O)N(CSP(OC)(OC)=S)N=1>[CH2:1]([O:3][C:4](=[O:22])[CH:5]([C:6]1[CH:7]=[CH:8][C:9]([S:12]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)(=[O:13])=[O:14])=[CH:10][CH:11]=1)[CH2:32][CH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1)[CH3:2]

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 2762531(Iodomethyl)cyclopentaneHCID 44473999[4-(4-Methyl-piperazine-1-sulfonyl)phenyl]acetic acid ethyl ester

Product 1

HCID 444735283-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 13709MethidathionSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of the title C compound, [4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-acetic acid ethyl ester (15 g, 0.046 mol) in a mixture of THF (60 mL) and DMTP (10 mL) is cooled to −78° C. under nitrogen. The resulting solution is stirred at −78° C. for 45 min and to this is added LDA (25.6 mL, 6.40 g, 0.059 mol, 25% solution in THF/Hexane). A solution of iodomethylcyclopentane (11.60 g, 0.055 mol) in a mixture of DMTP (12 mL) and THF (20 mL) is added over a period of 15 min at −78° C. and reaction mixture stirred at −78° C. for 3 h further, followed by stirring at 25° C. for 12 h. The reaction mixture is then quenched by the dropwise addition of saturated aqueous ammonium chloride solution (50 mL) and is concentrated in vacuo. The residue is diluted with water (50 mL) and extracted with ethyl acetate (3×100 mL). The organic solution is washed with a saturated aqueous sodium chloride (2×150 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Column chromatography over silica gel (60-120 mesh), using 50% ethyl acetate in hexane as an eluent to afford 3-cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic acid ethyl ester as a white solid: 1H NMR (400 MHz, CDCl3) δ 0.9-2.1 (m, 11H), 1.2 (t, J=7.1, 3H), 2.3 (s, 3H), 2.5 (br s, 4H), 3.0 (br s, 4H), 3.6 (m, 1H), 4.1 (q, J=7.1, 2H), 7.5 (d, J=8.3, 2H), 7.7 (d, J=8.3, 2H); MS 409 [M+1]+.

Workup

  1. additionis added over a period of 15 min at −78° C.
  2. customreaction mixture
  3. stirringstirred at −78° C. for 3 h further
  4. stirringby stirring at 25° C. for 12 h
  5. customThe reaction mixture is then quenched by the dropwise addition of saturated aqueous ammonium chloride solution (50 mL)
  6. concentrationis concentrated in vacuo
  7. additionThe residue is diluted with water (50 mL)
  8. extractionextracted with ethyl acetate (3×100 mL)
  9. washThe organic solution is washed with a saturated aqueous sodium chloride (2×150 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0ed93869943b407d8e19809bdf691d26
Source dataset
uspto-grants-2010_07
Patent number
US07750020B2

Linked notes

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