Methyl Ethyl Ketone → (3-{2-[4-(2,4-Dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl ester

HRID 2411586Notes

Reaction equation

HRID 2411586 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:27][CH2:26][CH2:25][S:24]3(=[O:29])=[O:28])=[CH:19][C:18]=2[OH:30])=[O:16])[CH2:11][CH2:10]1.[C:31]([O:35][C:36](=[O:42])[NH:37][CH2:38][CH2:39][CH2:40]Br)([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+].CC(=O)CC>O>[C:31]([O:35][C:36](=[O:42])[NH:37][CH2:38][CH2:39][CH2:40][O:30][C:18]1[CH:19]=[C:20]([N:23]2[CH2:27][CH2:26][CH2:25][S:24]2(=[O:29])=[O:28])[CH:21]=[CH:22][C:17]=1[C:15]([N:12]1[CH2:11][CH2:10][N:9]([C:3]2[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[CH3:1])[CH2:14][CH2:13]1)=[O:16])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 6569Methyl Ethyl KetoneHCID 10796Cesium carbonateHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 71252235[4-(2,4-Dimethylphenyl)piperazin-1-yl][4-(1,1-dioxo-1lambda6-isothiazolidin-2-yl)-2-hydroxyphenyl]methanone

Product 1

HCID 71252727(3-{2-[4-(2,4-Dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl esterYield 67.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of [4-(2,4-dimethylphenyl)piperazin-1-yl][4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-2-hydroxyphenyl]methanone (241 mg) described in Example 124, (3-bromopropyl)carbamic acid tert-butyl ester (200 mg) and cesium carbonate (548 mg) was added 2-butanone (4 mL), and the mixture was stirred with heating under reflux for 4 hr. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the solvent was evaporated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give (3-{2-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl ester (221 mg). The obtained (3-{2-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenoxy}propyl)carbamic acid tert-butyl ester (221 mg) was dissolved in dichloromethane (2 mL), trifluoroacetic acid (0.46 mL) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into ice water, the mixture was neutralized with sodium hydrogen carbonate and extracted with chloroform, and the solvent was evaporated. The obtained residue was purified by NH-coated silica gel column chromatography (ethyl acetate:methanol) to give the title compound (74 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 4 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. customthe solvent was evaporated
  5. customThe obtained residue was purified by column chromatography (ethyl acetate:hexane)

Sources & evidence

ORD record
ord-1adfcbacc13c4cc48301dca6ed7f8b9d
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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