4-Nitrobenzenesulfonyl chloride → ((2S,4R)-4-(3-chloropropyl)-5-oxopyrrolidin-2-yl)methyl 4-nitrobenzenesulfonate

HRID 2039951Notes

Reaction equation

HRID 2039951 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([CH2:10][OH:11])[NH:7][C:6]1=[O:12].[N+:13]([C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1)([O-:15])=[O:14].C(N(CC)CC)C.S(C1C=CC([N+]([O-])=O)=CC=1)([O-])(=O)=O>CN(C1C=CN=CC=1)C.C1COCC1.CCOC(C)=O>[N+:13]([C:16]1[CH:17]=[CH:18][C:19]([S:22]([O:11][CH2:10][C@@H:8]2[CH2:9][C@@H:5]([CH2:4][CH2:3][CH2:2][Cl:1])[C:6](=[O:12])[NH:7]2)(=[O:24])=[O:23])=[CH:20][CH:21]=1)([O-:15])=[O:14]

Participants

8

Reactant 4

HCID 74044-Nitrobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 4215492NosylateHCID 58011472HCID 58011472, compound

Product 1

HCID 58011487((2S,4R)-4-(3-chloropropyl)-5-oxopyrrolidin-2-yl)methyl 4-nitrobenzenesulfonateYield 86%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The (3R,5S)-3-(3-chloropropyl)-5-(hydroxymethyl)pyrrolidin-2-one (8.31 g, 43.4 mmol, 1.0 equiv), p-nitrobenzenesulfonylchloride (10.57 g, 47.7 mmol, 1.1 equiv) and DMAP (0.53 g, 4.4 mmol, 0.1 equiv) were added to a 500 mL round-bottom flask and dissolved in THF (100 mL) under nitrogen. Triethylamine (8.77 g, 12.1 mL, 86.7 mmol, 2.0 equiv) was added via syringe and the resulting solution stirred for 17 h at ambient temperature. After this time complete formation of the desired nosylate was observed by LC/MS analysis. The mixture was diluted with 50 mL of EtOAc and the amines quenched by addition of 100 mL of 1.0 M HCl. The layers were separated and the organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The pale yellow solid was washed with ether and residual solvent removed in vacuo. This afforded 14.02 g (86% yield) of ((2S,4R)-4-(3-chloropropyl)-5-oxopyrrolidin-2-yl)methyl 4-nitrobenzenesulfonate.

Workup

  1. customthe amines quenched by addition of 100 mL of 1.0 M HCl
  2. customThe layers were separated
  3. washthe organic layer washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. washThe pale yellow solid was washed with ether and residual solvent
  8. customremoved in vacuo

Sources & evidence

ORD record
ord-b6db6c19a575491b8006f0fd063a1a33
Source dataset
uspto-grants-2013_11
Patent number
US08580823B2

Reaction notes

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