Water → HCID 20815203, compound

HRID 896449Notes

Reaction equation

HRID 896449 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[S:7]1(=[O:17])=[O:16].C(N(C(C)C)C(C)C)C.[CH2:27]([NH:34][CH2:35][CH:36]1[CH2:45][CH:44]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[O:37]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O>CN1CCCC1=O>[CH2:27]([N:34]([CH2:35][CH:36]1[CH2:45][CH:44]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:48])[CH3:49])[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[O:37]1)[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[S:7]1(=[O:17])=[O:16])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 107817741,1-Dioxido-2-(4-bromobutyl)-1,2-benzisothiazol-3(2H)-oneHCID 22350904HCID 22350904, compound

Product 1

HCID 20815203HCID 20815203, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

380 mg (1.19 mmol) of 2-(4-bromobutyl)-1,1-dioxo-1,2-dihydro-1λ6-benzo[d]isothiazol-3-one and 263 μl (1.51 mmol) of N-ethyldiisopropylamine are added to a solution of 224 mg (0.58 mmol) of benzyl-[4-(tert-butyldimethylsilanyloxy)chroman-2-ylmethyl]amine in 1.25 ml of dry N-methylpyrrolidinone. The reaction mixture is stirred at 120° C. for 3 hours. After cooling to room temperature, 2 ml of water are added, resulting in the precipitation of a dark, viscous product. The supernatant is decanted and the residue is washed twice with in each case 1.5 ml of water. The product is then dissolved in 3 ml of dichloromethane, the residue water is removed by drying and the solution is evaporated to dryness. The crude product is purified by HPLC chromatography under the following conditions: column Nucleosil® 100 C-18, 125×16 mm (particle size 7 μm), column temperature room temperature, mobile phase 85% acetonitrile/15% water (v/v), flow rate 6 ml/min, UV detection at 230 nm. The product-containing fractions are combined and evaporated to dryness. The residue is dissolved in 2.5 ml of ethanol and 6 ml of acetone and again evaporated to dryness. The product is dried in a desiccator over blue gel.

Workup

  1. temperatureAfter cooling to room temperature
  2. customresulting in the precipitation of a dark, viscous product
  3. customThe supernatant is decanted
  4. washthe residue is washed twice with in each case 1.5 ml of water
  5. dissolutionThe product is then dissolved in 3 ml of dichloromethane
  6. customthe residue water is removed
  7. customby drying
  8. customthe solution is evaporated to dryness
  9. customThe crude product is purified by HPLC chromatography under the following conditions
  10. customcolumn Nucleosil® 100 C-18, 125×16 mm (particle size 7 μm), column temperature room temperature, mobile phase 85% acetonitrile/15% water (v/v), flow rate 6 ml/min, UV detection
  11. customevaporated to dryness
  12. dissolutionThe residue is dissolved in 2.5 ml of ethanol
  13. custom6 ml of acetone and again evaporated to dryness
  14. customThe product is dried in a desiccator over blue gel

Sources & evidence

ORD record
ord-8cba789d52c94e0aaed27c8fbcd50188
Source dataset
uspto-grants-2005_07
Patent number
US06919360B2

Reaction notes

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