(4S)-(4-methyl-2,5-dioxoimidazolidin-4-yl)methanesulphonyl chloride → (5S)-5-methyl-5-[({4-[4-(2,2,3,3-tetrafluoropropoxy)phenoxy]-piperidin-1-yl}sulphonyl)methyl]imidazolidine-2,4-dione

HRID 1091988Notes

Reaction equation

HRID 1091988 reaction equation
[CH3:1][C@@:2]1([CH2:9][S:10](Cl)(=[O:12])=[O:11])[C:6](=[O:7])[NH:5][C:4](=[O:8])[NH:3]1.Cl.[F:15][C:16]([F:35])([CH:32]([F:34])[F:33])[CH2:17][O:18][C:19]1[CH:31]=[CH:30][C:22]([O:23][CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:21][CH:20]=1>ClCCl.C(N(CC)CC)C>[CH3:1][C@:2]1([CH2:9][S:10]([N:27]2[CH2:28][CH2:29][CH:24]([O:23][C:22]3[CH:21]=[CH:20][C:19]([O:18][CH2:17][C:16]([F:15])([F:35])[CH:32]([F:34])[F:33])=[CH:31][CH:30]=3)[CH2:25][CH2:26]2)(=[O:12])=[O:11])[NH:3][C:4](=[O:8])[NH:5][C:6]1=[O:7]

Participants

5

Reactant 2

HCID 16738713(4S)-(4-methyl-2,5-dioxoimidazolidin-4-yl)methanesulphonyl chlorideHCID 866246544-{4-(2,2,3,3-Tetrafluoropropoxy)phenoxy]-piperidine hydrochloride

Product 1

HCID 11605689(5S)-5-methyl-5-[({4-[4-(2,2,3,3-tetrafluoropropoxy)phenoxy]-piperidin-1-yl}sulphonyl)methyl]imidazolidine-2,4-dioneYield 24.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

[(4S)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulphonyl chloride (0.453 g) was added to a solution of 4-{4-(2,2,3,3-tetrafluoropropoxy)phenoxy]-piperidine hydrochloride (0.69 g) in dichloromethane (25 ml) and triethylamine (1.7 ml) at ambient temperature. Stirred for 16 hours and evaporated to dryness. The residue was purified by column chromatography (using λ230 nm as the detecting wavelength) eluting with a 0-10% methanol and dichloromethane. Yielded a solid product, which was dried under vacuum at 50° C. to yield the title compound (0.24 g). NMR Spectrum: (DMSOd6) δ 10.7 (s, 1H), 8.0 (s, 1H), 6.95 (m, 4H), 6.6 (tt, 1H), 4.5 (m, 2H), 4.4 (m, 1H), 3.5 (d, 1H), 3.3 (m, 3H), 3.1 (m, 2H), 1.9 (m, 2H), 1.7 (m, 2H), 1.35 (s, 3H). Mass Spectrum M−H− 495.89

Workup

  1. customevaporated to dryness
  2. customThe residue was purified by column chromatography (
  3. washeluting with a 0-10% methanol and dichloromethane
  4. customYielded a solid product, which
  5. customwas dried under vacuum at 50° C.

Sources & evidence

ORD record
ord-bfe0875a13814150bce4117d70bc0134
Source dataset
uspto-grants-2012_03
Patent number
US08129412B2

Reaction notes

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