Carbon Dioxide → N-[(1S,2R)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide

HRID 2360332Notes

Reaction equation

HRID 2360332 reaction equation
[Br:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C@H:7]2[CH2:11][CH2:10][CH2:9][C@H:8]2[NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=[CH:4][CH:3]=1.C(=O)=O>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C@@H:7]2[CH2:11][CH2:10][CH2:9][C@@H:8]2[NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=[CH:19][CH:20]=1

Participants

4

Reactant 2

HCID 280Carbon DioxideHCID 67193989cis-N-[2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide2×

Product 1

HCID 67195844N-[(1S,2R)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Separation of the enantiomers comprising cis-N-[2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide (1.586 g, 4.38 mmol) was carried out by chiral chromatography. Column: Chiralpak® AD-H, 2.1×25 cm, 5 μm; Mobile phase: 75:25 carbon dioxide: methanol; Flow rate: 65 g/min. The first-eluting compound was enantiomer N-[(1R,2S)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide (767 mg, 2.12 mmol, 48%) and the second-eluting peak provided desired product N-[(1S,2R)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide upon removal of solvent in vacuo. Yield: 758 mg, 2.09 mmol, 48%. The absolute stereochemistry of these enantiomers was assigned by analogy to their higher homologues (see Example 7). The title compound, synthesized in the following step, proved significantly more potent than its enantiomer (prepared in the same way from N-[(1R,2S)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide. On this basis, the (1S,2R) configuration was assigned to N-[(1S,2R)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide. MS (APCI) m/z 364.2 (M+1). 1H NMR (500 MHz, CDCl3) δ 1.35 (d, J=6.8 Hz, 3H), 1.38 (d, J=6.8 Hz, 3H), 1.64 (m, 1H), 1.79-1.98 (m, 4H), 2.12 (m, 1H), 3.13 (septet, J=6.8 Hz, 1H), 3.86 (m, 1H), 4.59 (m, 1H), 4.63 (d, J=9.5 Hz, 1H), 6.78 (d, J=9.0 Hz, 2H), 7.39 (d, J=9.1 Hz, 2H). Data for N-[(1R,2S)-2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide: MS (APCI) m/z 362.2, 364.2 (M+1). 1H NMR (500 MHz, CDCl3) δ 1.35 (d, J=6.8 Hz, 3H), 1.38 (d, J=6.8 Hz, 3H), 1.58-1.68 (m, 1H), 1.78-1.97 (m, 4H), 2.12 (m, 1H), 3.13 (septet, J=6.8 Hz, 1H), 3.86 (m, 1H), 4.59 (m, 1H), 4.64 (d, J=9.5 Hz, 1H), 6.78 (d, J=9.1 Hz, 2H), 7.39 (d, J=9.0 Hz, 2H).

Workup

  1. customSeparation of the enantiomers

Sources & evidence

ORD record
ord-0c5963be301d400199bb46bc532312f4
Source dataset
uspto-grants-2014_04
Patent number
US08686043B2

Reaction notes

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