Hydrochloric Acid → HCID 18395010, compound

HRID 445037Notes

Reaction equation

HRID 445037 reaction equation
Cl.[CH2:2]([N:5]1[C@@H:10]([CH3:11])[CH2:9][N:8]([C@@H:12]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][Si](C(C)(C)C)(C)C)[CH:26]=2)[C:13]2[CH:18]=[CH:17][C:16]([S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[C@H:7]([CH3:39])[CH2:6]1)[CH:3]=[CH2:4].O>C1COCC1>[CH2:2]([N:5]1[C@@H:10]([CH3:11])[CH2:9][N:8]([C@@H:12]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)[C:13]2[CH:14]=[CH:15][C:16]([S:19]([N:22]([CH3:24])[CH3:23])(=[O:20])=[O:21])=[CH:17][CH:18]=2)[C@H:7]([CH3:39])[CH2:6]1)[CH:3]=[CH2:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 69330500HCID 69330500, compound

Product 1

HCID 18395010HCID 18395010, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Aqueous hydrochloric acid (3 M, 7 mL) was added to a solution of 4-{(R)-((2R,5S)-4-allyl-2,5-dimethyl-piperazin-1-yl)-[3-(tert-butyl-dimethylsilanyloxy)-phenyl]-methyl}-N,N-dimethyl-benzenesulfonamide (1.3 g) in THF (15 mL). The mixture was stirred at room temperature overnight. Water (15 mL) was added to the reaction. The reaction mixture was extracted with diethyl ether (25 mL×3). The remaining H2O layer was neutralized by 10% aqueous NaOH to pH=8-9 and then extracted by EtOAc (30 mL×3). The combined EtOAc layers were washed by water (20 mL×3) and brine (20 mL×1), dried over Na2SO4 and concentrated to give 0.83 g of crude product. The crude product was purified by silica gel chromatography conducted on CombiFlash™ Sq 16x (gradient: 100% CH2Cl2 to 7% MeOH in CH2Cl2) to give 4-[(R)-((2R,5S)-4-allyl-2,5-dimethylpiperazin-1-yl)-(3-hydroxy-phenyl)methyl]-N,N-dimethylbenzenesulfonamide (720 mg; 70%). 1H NMR (300 MHz, CDCl3) δ 7.71 (d, 2H, J=8.5 Hz), 7.35 (d, 2H, J=8.5 Hz), 7.14 (dd, 1H, J=8.0, 8.0 Hz), 6.89 (bs, 1H), 6.85 (d, 1H, J=8.0 Hz), 6.68 (d, 1H, J=8.0, 2.5 Hz), 5.83 (1H, m), 5.24-5.12 (m, 3H), 3.32 (dd, 1H, J=13.5, 5.0 Hz), 2.86 (dd, 1H, J=13.5, 8.0 Hz), 2.78 (dd, 1H, J=11.5, 3.0 Hz), 2.72 (s, 6H), 2.65 (dd, 1H, J=11.0, 2.5 Hz), 2.51 (m, 2H), 2.14 (dd, 1H, J=11.5, 9.0 Hz), 1.81 (dd, 1H, J=11.0, 9.5 Hz), 1.16 (d, 3H, J=6.0 Hz), 0.98 (d, 3H, J=6.0 Hz); MS (FAB, glycerol) m/z: 444 (M++H), 290, 153; Found: C, 58.32; H, 6.66; N, 8.18. Calc. (C24H33N3O3S 0.8 CH2Cl2): C, 58.23; H, 6.82; N, 8.21.

Workup

  1. extractionThe reaction mixture was extracted with diethyl ether (25 mL×3)
  2. extractionextracted by EtOAc (30 mL×3)
  3. washThe combined EtOAc layers were washed by water (20 mL×3) and brine (20 mL×1)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give 0.83 g of crude product
  7. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f455a31ae0a74a43bfa665f0db049f0d
Source dataset
uspto-grants-2013_07
Patent number
US08476280B2

Reaction notes

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