Methyl vinyl sulfone → HCID 44517931, compound

HRID 1972214Notes

Reaction equation

HRID 1972214 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)[CH2:16][NH:15][C:14]3=[O:28])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH:33]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH2:34].[NH4+].[Cl-]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:26])([F:25])[F:27])[CH:19]=4)[CH2:16][N:15]([CH2:34][CH2:33][S:35]([CH3:38])(=[O:37])=[O:36])[C:14]3=[O:28])=[CH:11][CH:12]=2)=[CH:29][CH:30]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=4)[CH2:16][NH:15][C:14]3=[O:28])=[CH:11][CH:12]=2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 19354Methyl vinyl sulfoneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59485924(S)-1-(4-(4-chlorophenoxy)phenyl)-5-(3-(trifluoromethyl)phenyl)imidazolidin-2-one

Product 2

HCID 44517931HCID 44517931, compoundYield 63%HCID 59485924(S)-1-(4-(4-chlorophenoxy)phenyl)-5-(3-(trifluoromethyl)phenyl)imidazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (S)-1-[4-(4-chloro-phenoxy)-phenyl]-5-(3-trifluoromethyl-phenyl)-imidazolidin-2-one (1.5 g, 3.47 mmol) in anhydrous DMF (20 mL) is cooled down to 0° C. in an ice bath when NaH (194 mg, 60% in mineral oil, 4.86 mmol) is added into the solution portion wise. After the addition, the mixture is stirred at 0° C. for 10 min when a solution of vinyl methylsulfone (736 mg, 6.94 mmol) in DMF (5 mL) is added into the mixture. The resulted mixture is allowed to warm up to room temperature and stir for 1 h. The mixture is then poured into 10% NH4Cl aqueous solution (˜300 mL) and extracted with EtOAc (3×100). The combined organic layer is washed with brine and dried (MgSO4). After removing the drying agent, the solution is concentrated and purified by flash column chromatography (silica gel, EtOAc/hexane 0%˜100%) to provide the desired product (S)-3-[4-(4-chloro-phenoxy)-phenyl]-1-(2-methanesulfonyl-ethyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one as white solid (1.18 g, 63%) with the recovery of the starting material (S)-1-[4-(4-chloro-phenoxy)-phenyl]-5-(3-trifluoromethyl-phenyl)-imidazolidin-2-one (˜300 mg). 1H NMR (CDCl3, 400 MHz) δ 7.45˜7.58 (m, 4H), 7.29 (d, 2H), 7.23 (d, 2H), 6.87 (m, 4H), 5.27 (dd, 1H), 4.07 (t, 1H), 3.80˜4.10 (m, 2H), 3.28˜3.40 (m, 3H), 3.01 (s, 3H); HPLC-MS calculated for C25H22ClF3N2O4S (M+H+) 539.1, found 539.1.

Workup

  1. additionis added into the solution portion wise
  2. additionAfter the addition
  3. additionis added into the mixture
  4. extractionextracted with EtOAc (3×100)
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried (MgSO4)
  7. customAfter removing the drying agent
  8. concentrationthe solution is concentrated
  9. custompurified by flash column chromatography (silica gel, EtOAc/hexane 0%˜100%)

Sources & evidence

ORD record
ord-e037fec99fb94e3c912c5e6ae4d5676c
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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