Acetic Acid → {(2S)-2-(3,4-Dichlorophenyl)-4-[3-(1-oxidothiomorpholin-4-yl)azetidin-1-yl]butyl}methylamine diacetate

HRID 749422Notes

Reaction equation

HRID 749422 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6]([C@H:11]([CH2:15][CH2:16][N:17]2[CH2:20][CH:19]([N:21]3[CH2:26][CH2:25][S:24][CH2:23][CH2:22]3)[CH2:18]2)[CH2:12][NH:13][CH3:14])[CH:7]=[CH:8][C:9]=1[Cl:10].OO.[C:29]([OH:32])(=[O:31])[CH3:30]>>[C:29]([O-:32])(=[O:31])[CH3:30].[NH4+:13].[C:29]([OH:32])(=[O:31])[CH3:30].[C:29]([OH:32])(=[O:31])[CH3:30].[Cl:3][C:4]1[CH:5]=[C:6]([C@H:11]([CH2:15][CH2:16][N:17]2[CH2:18][CH:19]([N:21]3[CH2:22][CH2:23][S:24](=[O:31])[CH2:25][CH2:26]3)[CH2:20]2)[CH2:12][NH:13][CH3:14])[CH:7]=[CH:8][C:9]=1[Cl:10]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 68979570[(2S)-2-(3,4-dichlorophenyl)-4-(3-thiomorpholin-4-ylazetidin-1-yl)butyl]methylamine dihydrochloride

Product 2

HCID 517165Ammonium AcetateHCID 86606877{(2S)-2-(3,4-Dichlorophenyl)-4-[3-(1-oxidothiomorpholin-4-yl)azetidin-1-yl]butyl}methylamine diacetateYield 49%

Procedure

[(2S)-2-(3,4-Dichlorophenyl)-4-(3-thiomorpholin-4-ylazetidin-1-yl)butyl]methylamine hydrochloride (see Method 1; 270 mg, 0.54 mmol) was dissolved in acetic acid and to the resultant solution was added hydrogen peroxide (0.05 mL of 35% aqueous solution, 0.54 mmol). The mixture was stirred at room temperature for 2.5 h and the solvent was removed by evaporation. The residue was dissolved in ethanol (50 mL) and to the resultant solution was added MP-Carbonate resin (0.86 g of 3.18 mmol/g polymer-bound resin). The mixture was stirred for 30 min and then filtered whereupon the solvent was removed by evaporation. The product was purified by reversed phase chromatography using a mixture of acetonitrile and 0.1 M ammonium acetate aq. There was obtained 140 mg (49%) of {(2S)-2-(3,4-Dichlorophenyl)-4-[3-(1-oxidothiomorpholin-4-yl)azetidin-1-yl]butyl}methylamine diacetate. 1H NMR (400 MHz, CDCl3): 1.6-1.8 (m, 2H), 1.9 (s, 6H), 2.3-2.4 (m, 1H), 2.4-2.5 (m, 7H), 2.7-3.0 (m, 10H), 3.1 (m, 1H), 3.6 (m, 2H), 7.0 (dd, 1H), 7.2 (d, 1H), 7.3 (d, 1H), 8.2 (s, 2H); LCMS: m/z 404 (M+1)+.

Workup

  1. customthe solvent was removed by evaporation
  2. dissolutionThe residue was dissolved in ethanol (50 mL) and to the resultant solution
  3. additionwas added MP-Carbonate resin (0.86 g of 3.18 mmol/g polymer-bound resin)
  4. stirringThe mixture was stirred for 30 min
  5. filtrationfiltered whereupon the solvent
  6. customwas removed by evaporation
  7. customThe product was purified by reversed phase chromatography
  8. additiona mixture of acetonitrile

Sources & evidence

ORD record
ord-8b74534f63dd4021a4d3d23f5f8101ec
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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