1-[Bis(4-chlorophenyl)methyl]azetidin-3-one → HCID 178527395, compound

HRID 18071Notes

Reaction equation

HRID 18071 reaction equation
CC(C)([O-])C.[K+].[CH3:7][S:8]([CH2:11][C:12]1[CH2:13][CH2:14][N:15]([C:18](=[S:20])[OH:19])[CH2:16][CH:17]=1)(=[O:10])=[O:9].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=2)[N:29]2[CH2:32][C:31](=[O:33])[CH2:30]2)=[CH:24][CH:23]=1>O1CCCC1.O>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=2)[N:29]2[CH2:30][C:31]([CH2:7][S:8]([CH2:11][C:12]3[CH2:17][CH2:16][N:15]([C:18](=[S:20])[OH:19])[CH2:14][CH:13]=3)(=[O:9])=[O:10])([OH:33])[CH2:32]2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 225066481-[Bis(4-chlorophenyl)methyl]azetidin-3-one2×HCID 23665647Potassium tert-butoxideHCID 178504868HCID 178504868, compound

Product 1

HCID 178527395HCID 178527395, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The phenolic ester of 4-({1-[bis(4-chloro-phenyl)methyl]-3-hydroxyazetidin-3-yl}methyl-sulfonylmethyl)-3,6-dihydro-2H-pyridine-1-carbothioic acid is prepared in the following manner: 0.52 g of potassium tert-butoxide is added to a mixture of 0.72 g of the phenolic ester of 4-methylsulfonylmethyl-3,6-dihydro-2H-pyridine-1-carbothioic acid and 0.708 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 15 cm3 of dry tetrahydrofuran cooled under an inert atmosphere to −78° C. The reaction mixture is stirred at −78° C. for 4 hours and then 0.354 g of 1-[bis(4-chlorophenyl)-methyl]azetidin-3-one are added. After two hours at −78° C., the temperature is allowed to return to 20° C. The reaction mixture is diluted in 100 cm3 of water and then the tetrahydrofuran is evaporated off under 2.7 kPa at 40° C. The aqueous phase is extracted with twice 100 cm3 of ethyl acetate. The organic extracts are combined and dried over magnesium sulfate, concentrated under 2.7 kPa at 40° C. The residue obtained is chromatographed on silica (200 g of silica, Amicon, 20-45 μm, porosity 60 Angstroem, column 5 cm in diameter), eluting with a cyclohexane:ethyl acetate (6:4 by volume) mixture. The fractions with an Rf=11/64 (cyclohexane:ethyl acetate 6:4, silica plate, Merck reference 1.05719, Merck KGaA, 64721 Darmstatd, Germany) are combined and concentrated under 2.7 kPa at 40° C. to give 240 mg of the phenolic ester of 4-({1-[bis(4-chlorophenyl)methyl]-3-hydroxyazetidin-3-yl}methylsulfonylmethyl)-3,6-dihydro-2H-pyridine-1-carbothioic acid.

Workup

  1. waitAfter two hours at −78° C.
  2. customto return to 20° C
  3. customthe tetrahydrofuran is evaporated off under 2.7 kPa at 40° C
  4. extractionThe aqueous phase is extracted with twice 100 cm3 of ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under 2.7 kPa at 40° C
  7. customThe residue obtained
  8. customis chromatographed on silica (200 g of silica, Amicon, 20-45 μm, porosity 60 Angstroem, column 5 cm in diameter)
  9. washeluting with a cyclohexane:ethyl acetate (6:4 by volume) mixture
  10. concentrationconcentrated under 2.7 kPa at 40° C.

Sources & evidence

ORD record
ord-b2f927d9ed28409c8cf69979c7121557
Source dataset
uspto-grants-2010_06
Patent number
US07741316B2

Reaction notes

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