Hydrochloric Acid → HCID 18395010, compound

HRID 2036175Notes

Reaction equation

HRID 2036175 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>O1CCCC1>[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

3 N HCl (7 mL) was added to the solution of 4-{(R)-((2R,5S)-4-allyl-2,5-dimethylpiperazin-1-yl)[3-(tert-butyl-dimethylsilanyloxy)-phenyl]methyl}-N,N-dimethylbenzenesulfonamide (1.3 g) in tetrahydrofuran (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 water layer was neutralized by 10% aqueous NaOH to pH=8-9 and then extracted with ethyl acetate (30 mL×3). The combined ethyl acetate layers were washed with water (20 mL×3) and brine (20 mL), dried over sodium sulfate and concentrated to give 0.83 g of crude product. The crude product was purified by silica gel chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% CH2Cl2 to 7% MeOH in CH2Cl2) to give 4-[(R)-((2R,5S)-4-allyl-2,5-dimethylpiperazin-1-yl)(3-hydroxyphenyl)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 with ethyl acetate (30 mL×3)
  3. washThe combined ethyl acetate layers were washed with water (20 mL×3) and brine (20 mL)
  4. dry with materialdried over sodium sulfate
  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-42e14614f1d74c268cc234c8986f03c0
Source dataset
uspto-grants-2013_11
Patent number
US08575169B2

Reaction notes

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