Methanesulfonyl chloride → Methyl 5-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}methylsulfonylmethyl)thien-2-ylcarboxylate

HRID 18064Notes

Reaction equation

HRID 18064 reaction equation
[CH3:1][S:2]([CH2:5][C:6]1[S:10][C:9]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:7]=1)(=[O:4])=[O:3].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:23]2[CH2:26][C:25](=O)[CH2:24]2)=[CH:18][CH:17]=1.CC(C)([O-])C.[K+].CS(Cl)(=O)=O>O1CCCC1.C(OCC)C.O>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([CH:22]([C:19]2[CH:18]=[CH:17][C:16]([Cl:15])=[CH:21][CH:20]=2)[N:23]2[CH2:26][C:25](=[CH:1][S:2]([CH2:5][C:6]3[S:10][C:9]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:7]=3)(=[O:4])=[O:3])[CH2:24]2)=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 17908444Methyl 5-(methylsulfonylmethyl)thiophene-2-carboxylateHCID 225066481-[Bis(4-chlorophenyl)methyl]azetidin-3-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 68585605Methyl 5-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}methylsulfonylmethyl)thien-2-ylcarboxylateYield 15.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

Methyl 5-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}methylsulfonylmethyl)thien-2-yl-carboxylate may be obtained in the following manner: 5.15 g of methyl 5-(methylsulfonylmethyl)thien-2-ylcarboxylate are added, at room temperature under an argon atmosphere, to a solution of 6.12 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 200 cm3 of tetrahydrofuran and then the suspension obtained is cooled to −70° C. There are successively added 2.47 g of potassium tert-butoxide, and then after 1 hour 30 min at this temperature a solution of 1.7 cm3 of methylsulfonylchloride in 8 cm3 of ethyl ether over 2 minutes. The reaction medium is maintained for 1 hour at −70° C. and then the temperature is allowed to rise to around 20° C. before pouring in 80 cm3 of distilled water. The tetrahydrofuran is expelled under reduced pressure and the aqueous residue obtained is extracted with 500 cm3 of dichloromethane. The mixture is separated after settling, the organic phase is washed with 3 times 80 cm3 of distilled water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is purified by flash chromatography on silica gel [eluent: cyclohexane/ethyl acetate (70/30 by volume)]. 1.6 g of methyl 5-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}methylsulfonylmethyl)thien-2-ylcarboxylate are obtained in the form of a cream-colored foam.

Workup

  1. customthe suspension obtained
  2. temperatureThe reaction medium is maintained for 1 hour at −70° C.
  3. customto rise to around 20° C.
  4. customthe aqueous residue obtained
  5. extractionis extracted with 500 cm3 of dichloromethane
  6. customThe mixture is separated
  7. washthe organic phase is washed with 3 times 80 cm3 of distilled water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe residue obtained
  12. customis purified by flash chromatography on silica gel [eluent: cyclohexane/ethyl acetate (70/30 by volume)]

Sources & evidence

ORD record
ord-a9a916c5aa6346c5940188a4a4ef7bbc
Source dataset
uspto-grants-2010_06
Patent number
US07741316B2

Reaction notes

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