Hydrochloric Acid → 3-[(3-Aminophenyl)(methylsulfonyl)methylene]-1-benzhydrylazetidine

HRID 25176Notes

Reaction equation

HRID 25176 reaction equation
[CH:1]([N:14]1[CH2:17][C:16](=[C:18]([S:28]([CH3:31])(=[O:30])=[O:29])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-])=O)[CH:20]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C(O)C.O1CCCC1.[Fe]>[NH2:25][C:21]1[CH:20]=[C:19]([C:18](=[C:16]2[CH2:15][N:14]([CH:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:17]2)[S:28]([CH3:31])(=[O:30])=[O:29])[CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 22565379HCID 22565379, compound

Product 1

HCID 225653763-[(3-Aminophenyl)(methylsulfonyl)methylene]-1-benzhydrylazetidineYield 53.7%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.34 g of 1-benzhydryl-3-[(methylsulfonyl)(3-nitrophenyl)methylene]azetidine, 16 cm3 of 1 N hydrochloric acid in 8 cm3 of ethanol and 16 cm3 of tetrahydrofuran is heated under reflux. 0.17 g of iron powder is added and the reflux is maintained for 3 hours. The mixture is then cooled to room temperature and the insoluble matter is filtered off. The solution is taken up in 10 cm3 of 1 N sodium hydroxide and 50 cm3 of a saturated aqueous sodium chloride solution. The aqueous phase is extracted with 3 times 40 cm3 of dichloromethane, the extracts are combined, dried over sodium sulfate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 30 cm) at a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (50/50 by volume) as eluent, collecting 20 cm3 fractions. Fractions 13 to 31 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is crystallized from 15 cm3 of ethyl ether. 0.17 g of 3-[(3-aminophenyl)(methylsulfonyl)methylene]-1-benzhydrylazetidine is obtained melting at 197° C. [NMR spectrum in DMSO-d6, T=300K, δ in ppm (250 MHz): 2.95 (3H, s, SCH3), 3.80 (2H, s, NCH2), 4.20 (2H, s, NCH2), 4.75 (1H, s, NCH), 5.25 (2H, s, NH2), 6.55 (3H, m, 3CH arom.), 7.05 (1H, t, J=7 Hz, CH arom.), 7.20 (2H, t, J=7 Hz, 2CH arom.), 7.30 (4H, t, J=7 Hz, 4CH arom.), 7.45 (4H, d, J=7 Hz, 4CH arom.)].

Workup

  1. temperatureis heated
  2. temperatureunder reflux
  3. temperaturethe reflux is maintained for 3 hours
  4. filtrationthe insoluble matter is filtered off
  5. extractionThe aqueous phase is extracted with 3 times 40 cm3 of dichloromethane
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is purified on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 30 cm) at a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (50/50 by volume) as eluent
  9. customcollecting 20 cm3 fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe solid obtained
  12. customis crystallized from 15 cm3 of ethyl ether

Sources & evidence

ORD record
ord-60721e8b03f9484c801d725d39c2c287
Source dataset
uspto-grants-2005_02
Patent number
US06858603B2

Reaction notes

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