Acetic Acid → HCID 10207252, compound

HRID 25184Notes

Reaction equation

HRID 25184 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]#[N:25])[CH:19]=3)[S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10]2)=[CH:4][CH:3]=1.C(O)(=[O:35])C>Cl.C(O)C>[Cl:32][C:29]1[CH:28]=[CH:27][C:26]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24](=[O:35])[NH2:25])[CH:19]=3)[S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10]2)=[CH:31][CH:30]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 10116860HCID 10116860, compound

Product 1

HCID 10207252HCID 10207252, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4.5 g of 1-[bis(4-chlorophenyl)methyl]-3-[(3-cyanophenyl)(methylsulfonyl)methylene]azetidine in 50 cm3 of acetic acid and 50 cm3 of concentrated hydrochloric acid (d=1.18) is heated at 50° C. for 20 hours. The reaction medium is cooled to room temperature and concentrated to dryness under reduced pressure (2.7 kPa). The oil obtained is taken up in 100 cm3 of ethanol and then the solution is concentrated to dryness under reduced pressure (2.7 kPa). The residue is precipitated in 60 cm3 of ethyl ether. The solid obtained is purified by chromatography on a silica gel column (particle size 0.04-0.06 mm, diameter 25 cm, height 40 cm) at a nitrogen pressure of 0.5 bar with dichloromethane and then a dichloromethane and ethanol mixture (99.5/0.5 by volume) as eluent and collecting 30 cm3 fractions. Fractions 35 to 46 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is crystallized from 15 cm3 of ethyl ether. 0.2 g of 1-[bis(4-chlorophenyl)methyl]-3-[(3-carbamoylphenyl)(methylsulfonyl)methylene]azetidine is obtained in the form of a solid melting at 192° C. [NMR spectrum in DMSO-d6, T=300K, δ in ppm (300 MHz): 2.95 (3H, s, SCH3), 3.80 (2H, s, NCH2), 4.20 (2H, s, NCH2), 4.80 (1H, s, NCH), 7.35 (4H, d, J=7 Hz, 4CH arom.), 7.45 (5H, d, J=7 Hz, 4CH arom. and 2 CONH2), 7.50 (2H, m, 2CH arom.), 7.85 (2H, m, 2CH arom.)].

Workup

  1. temperatureThe reaction medium is cooled to room temperature
  2. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  3. customThe oil obtained
  4. concentrationthe solution is concentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is precipitated in 60 cm3 of ethyl ether
  6. customThe solid obtained
  7. customis purified by chromatography on a silica gel column (particle size 0.04-0.06 mm, diameter 25 cm, height 40 cm) at a nitrogen pressure of 0.5 bar with dichloromethane
  8. customa dichloromethane and ethanol mixture (99.5/0.5 by volume) as eluent and collecting 30 cm3 fractions
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe solid obtained
  11. customis crystallized from 15 cm3 of ethyl ether

Sources & evidence

ORD record
ord-19ff461fc1314ab89482f5a239bc50d0
Source dataset
uspto-grants-2005_02
Patent number
US06858603B2

Reaction notes

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