Hydroxyamine hydrochloride → HCID 10174606, compound

HRID 1013064Notes

Reaction equation

HRID 1013064 reaction equation
Cl.[NH2:2][OH:3].C([O-])(O)=O.[Na+].[F:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[N:17]2[CH2:22][CH2:21][N:20]([S:23]([C:26]3[CH:31]=[CH:30][C:29](/[CH:32]=[CH:33]/[C:34](Cl)=[O:35])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH2:19][CH2:18]2)=[CH:12][CH:11]=1>O1CCCC1.O>[F:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[N:17]2[CH2:22][CH2:21][N:20]([S:23]([C:26]3[CH:31]=[CH:30][C:29](/[CH:32]=[CH:33]/[C:34]([NH:2][OH:3])=[O:35])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH2:19][CH2:18]2)=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 57503234HCID 57503234, compound

Product 1

HCID 10174606HCID 10174606, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of hydroxylamine hydrochloride (0.18 g, 2.5 mmol) in tetrahydrofuran (5.0 mL) a solution of NaHCO3 (0.30 g, 3.5 mmol) in water (5 mL) was added and the resultant mixture was stirred at ambient temperature for 5 minutes. The reaction mixture was added to a solution of (E)-3-[4-({4-[bis(4-fluorophenyl)methyl]-1-piperazinyl}sulfonyl)phenyl]-2-propenoyl chloride (10b) (0.26 g) in tetrahydrofuran (5 mL) and the obtained mixture was stirred at ambient temperature for 0.5 hours. The mixture was poured into water (25 mL), extracted with ethyl acetate, the extract was washed with water, brine, and dried (Na2SO4). The solvent was removed and the residue was chromatographed on silica gel with chloroform-isopropanol (9:1) as eluent to give the title compound (0.087 g, 34%). M.p. 125-126° C. 1H NMR (DMSO-d6, HMDSO), δ: 2.26-2.42 (4H, m); 2.81-3.00 (4H, m); 4.39 (1H, s); 6.64 (1H, d, J=15.8 Hz); 7.07 (4H, t, J=8.6 Hz); 7.37 (4H, dd, J=8.4 and 5.6 Hz); 7.57 (1H, d, J=15.8 Hz); 7.74 (2H, d, J=8.0 Hz); 7.83 (2H, d, J=8.0 Hz); 9.19 (1H, s); 10.93 (1H, s). HPLC analysis on Alltima C18 column: impurities 2% (column size 4.6×150 mm; mobile phase acetonitrile-0.1M phosphate buffer (pH 2.5), 70:30; sample concentration 1.0 mg/ml; flow rate 1.0 mL/min; detector: UV 215 nm). Anal. Calcd for C26H25F2N3O4S*0.3 Et2O*0.2 iso-PrOH*0.1CHCl3 (an exhaustively dried material contains all the indicated traces of solvents (PMR)), %: C, 59.87; H, 5.35; N, 7.51; S, 5.73. Found, %: C, 59.85; H, 5.36; N, 7.29; S, 5.60.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. washthe extract was washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was removed
  6. customthe residue was chromatographed on silica gel with chloroform-isopropanol (9:1) as eluent

Sources & evidence

ORD record
ord-7039378a19a34335bd5e60038533ba76
Source dataset
uspto-grants-2011_07
Patent number
US07981895B2

Reaction notes

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