Cyclopropanesulfonyl chloride → Ethyl 4-(cyclopropanesulfonamido)-2-methylcyclopentanecarboxylate

HRID 1854419Notes

Reaction equation

HRID 1854419 reaction equation
[NH2:1][CH:2]1[CH2:6][CH:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:4]([CH3:12])[CH2:3]1.[CH:13]1([S:16](Cl)(=[O:18])=[O:17])[CH2:15][CH2:14]1>CN(C=O)C>[CH:13]1([S:16]([NH:1][CH:2]2[CH2:6][CH:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:4]([CH3:12])[CH2:3]2)(=[O:18])=[O:17])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 2760919Cyclopropanesulfonyl chlorideHCID 58010132Ethyl 4-amino-2-methylcyclopentanecarboxylate

Product 1

HCID 58009782Ethyl 4-(cyclopropanesulfonamido)-2-methylcyclopentanecarboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of ethyl 4-amino-2-methylcyclopentanecarboxylate (15.0 g, 88.0 mmol) in DMF (210 mL) was cooled to about 0° C. in an ice bath. TEA (30.5 mL, 219 mmol) was added and stirring was continued at about 0° C. for about 15 min and then cyclopropanesulfonyl chloride (12.3 g, 88.0 mmol, Matrix) was added drop-wise. The resulting solution was stirred at about 0° C. for about 2 h. The ice bath was removed and the reaction mixture continued stirring at ambient temperature for about 3 h. The reaction was concentrated under reduced pressure and EtOAc (200 mL) and water (100 mL) were added. The layers were separated and the organic layer was washed with saturated aqueous NaHCO3 (60 mL) and brine (60 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give a reddish brown oil. The crude material was purified by silica gel chromatography eluting with a gradient of 10-30% EtOAc in heptane to give ethyl 4-(cyclopropanesulfonamido)-2-methylcyclopentanecarboxylate (21.3 g, 88%) as a yellow oil: 1H NMR (CDCl3) δ 5.25 (d, J=9.9 Hz, 1H), 4.23-4.06 (m, 2H), 4.03-3.90 (m, 1H), 2.80 (td, J=3.1, 7.5 Hz, 1H), 2.46-2.30 (m, 2H), 2.29-2.14 (m, 2H), 1.97 (ddd, J=3.2, 4.2, 14.2 Hz, 1H), 1.42 (ddd, J=7.5, 11.5, 13.1 Hz, 1H), 1.29 (t, J=7.1 Hz, 3H), 1.20-1.14 (m, 2H), 1.02 (d, J=6.9 Hz, 3H), 1.00-0.96 (m, 2H).

Workup

  1. stirringThe resulting solution was stirred at about 0° C. for about 2 h
  2. customThe ice bath was removed
  3. stirringthe reaction mixture continued stirring at ambient temperature for about 3 h
  4. concentrationThe reaction was concentrated under reduced pressure and EtOAc (200 mL) and water (100 mL)
  5. additionwere added
  6. customThe layers were separated
  7. washthe organic layer was washed with saturated aqueous NaHCO3 (60 mL) and brine (60 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a reddish brown oil
  12. customThe crude material was purified by silica gel chromatography
  13. washeluting with a gradient of 10-30% EtOAc in heptane

Sources & evidence

ORD record
ord-ef91f8ae24e647218b5acf7c928b6d43
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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