Benzyl Bromide → 2-Benzyl-5-phenyl-4-[(4-phenylbutyl)amino]isothiazol-3(2H)-one 1,1-dioxide

HRID 2422038Notes

Reaction equation

HRID 2422038 reaction equation
C([N:5]1[C:9](=[O:10])[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:6]1(=[O:29])=[O:28])(C)(C)C.C(=O)([O-])[O-].[K+].[K+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C(O)(C(F)(F)F)=O>[CH2:36]([N:5]1[C:9](=[O:10])[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:6]1(=[O:28])=[O:29])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 114952832-tert-Butyl-5-phenyl-4-[(4-phenylbutyl)amino]isothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 116980342-Benzyl-5-phenyl-4-[(4-phenylbutyl)amino]isothiazol-3(2H)-one 1,1-dioxideYield 54.7%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
120 °C

Procedure

2-tert-Butyl-5-phenyl-4-[(4-phenylbutyl)amino]isothiazol-3(2H)-one 1,1-dioxide (Example 1) (0.150 g, 0.36 mmol) was dissolved in TFA (3 ml) and heated in a microwave reactor at 120° C. for 20 mins. The reaction mixture was concentrated and the residue was repeatedly dissolved in DCM and evaporated. The crude product was dissolved in dry MeCN (3 ml) and potassium carbonate (0.251 g, 1.82 mmol) and benzylbromide (0.075 g, 0.44 mmol) was added. The reaction mixture was heated at 120° C. for 15 mins and then at 130° C. for 5 mins in a microwave reactor. The reaction mixture was purified by silica gel column chromatography using a 90:10 mixture of hexane and EtOAc as eluant, to give the title compound (0.088 g, 54%). 1H NMR (500 MHz, CDCl3): δ 7.55-7.49 (m, 4H), 7.48-7.31 (m, 6H), 7.31-7.25 (m, 2H), 7.23-7.17 (m, 1H), 7.11-7.05 (m, 2H), 5.31-5.25 (m, 1H), 4.85 (s, 2H), 2.90-2.82 (m, 2H), 2.50-2.42 (m, 2H), 1.45-1.33 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 159.3, 141.7, 135.6, 134.6, 131.8, 130.0, 129.0, 128.9, 128.9, 128.6, 128.5, 128.5, 126.2, 125.1, 107.0, 44.2, 43.8, 35.4, 29.2, 28.3

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was repeatedly dissolved in DCM
  3. customevaporated
  4. dissolutionThe crude product was dissolved in dry MeCN (3 ml)
  5. temperatureThe reaction mixture was heated at 120° C. for 15 mins
  6. customThe reaction mixture was purified by silica gel column chromatography
  7. additiona 90:10 mixture of hexane and EtOAc as eluant

Sources & evidence

ORD record
ord-bc1c375cf2904603a4306da451af53aa
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

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