Benzenesulfonyl chloride → trans-1-Benzenesulfonyl-4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester

HRID 460273Notes

Reaction equation

HRID 460273 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][NH:6]1.[C:12]1([S:18](Cl)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>N1C=CC=CC=1.C(OCC)(=O)C>[CH3:2][O:3][C:4](=[O:11])[C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[S:18]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:20])=[O:19]

Participants

5

Reactant 2

HCID 7369Benzenesulfonyl chlorideHCID 114353194-Hydroxy-L-proline methyl ester hydrochloride

Product 1

HCID 18445902trans-1-Benzenesulfonyl-4-hydroxy-pyrrolidine-2-carboxylic acid methyl esterYield 73.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 250 mL round bottom flask was dissolved 10.0 g (55 mmol) of trans-4-hydroxyproline methyl ester hydrochloride 14 (Bachem) in 100 mL anhydrous pyridine at 0° C. with stirring to give a cloudy white mixture. To this was added 7.9 mL (62 mmol, 1.1 equiv.) of benzenesulfonyl chloride in four portions over 15 minutes to give a bright yellow mixture. This reaction mixture was stirred under a CaCl2 drying tube at 4° C. (cold room) overnight, then concentrated in vacuo, and the residue dissolved in ethyl acetate (˜200 mL.) The solution was washed with 1 N HCl (three times), with H2O, 1 N NaOH (three times), then brine, and the organic solution was dried (MgSO4), filtered, and concentrated to give a yellow oil. This was dissolved in ethyl acetate, loaded onto silica, and eluted with 3:2 ethyl acetate/hexanes to give 11.5 g (40.3 mmol, 73%) of compound 15 as a white crystalline solid. 1H-NMR (400 MHz, CDCl3, δ ppm) 7.85 (dt, J=2 Hz, 7 Hz, 2H), 7.57 (tt, J=1 Hz, 8 Hz, 1H), 7.49 (td, J=2 Hz, 7 Hz, 2H), 4.41 (br s, 1H), 4.37 (t, J=8 Hz, 1H), 3.70 (s, 3H), 3.57 (dd, J=4 Hz, 11 Hz, 1H), 3.37 (dt, J=2 Hz, 11 Hz, 1H), 2.17 (m, 2H), 2.06 (m, 1H); 13C-NMR (400 MHz, CDCl3, δ ppm) 173.01, 138.05, 133.43, 129.42, 128.05, 70.37, 59.85, 56.83, 52.99, 39.81; m/z: 286 (M+1)+. See, for example, DiCesare, P., et al.; J. Med. Chem.; 35(22), pp. 4205–4213 (1992), which is incorporated by reference in its entirety.

Workup

  1. customto give a cloudy white mixture
  2. customto give a bright yellow mixture
  3. stirringThis reaction mixture was stirred under a CaCl2 drying tube at 4° C. (cold room) overnight
  4. concentrationconcentrated in vacuo
  5. dissolutionthe residue dissolved in ethyl acetate (˜200 mL.) The solution
  6. washwas washed with 1 N HCl (three times), with H2O, 1 N NaOH (three times)
  7. dry with materialbrine, and the organic solution was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a yellow oil
  11. washeluted with 3:2 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-c048c26b73844e7e8c8760f56ab0846e
Source dataset
uspto-grants-2007_03
Patent number
US07196112B2

Reaction notes

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