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

HRID 218436Notes

Reaction equation

HRID 218436 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-42cebf58dfba42ba9c6f8390f04bd2d8
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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