Ammonium Chloride → Ethyl 4-(cyclopropanesulfonamido)-2-ethyl-1-fluorocyclopentanecarboxylate

HRID 1969518Notes

Reaction equation

HRID 1969518 reaction equation
[CH:1]1([S:4]([NH:7][CH:8]2[CH2:12][CH:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:10]([CH2:18][CH3:19])[CH2:9]2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.[F:28]N(S(C1C=CC=CC=1)(=O)=O)S(C1C=CC=CC=1)(=O)=O.[NH4+].[Cl-]>C1COCC1>[CH:1]1([S:4]([NH:7][CH:8]2[CH2:12][C:11]([F:28])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:10]([CH2:18][CH3:19])[CH2:9]2)(=[O:6])=[O:5])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 2724682Lithium diisopropylamideHCID 58558091Ethyl 4-(cyclopropanesulfonamido)-2-ethylcyclopentanecarboxylate

Product 1

HCID 67217285Ethyl 4-(cyclopropanesulfonamido)-2-ethyl-1-fluorocyclopentanecarboxylateYield 61.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of ethyl 4-(cyclopropanesulfonamido)-2-ethylcyclopentanecarboxylate (0.630 g, 2.18 mmol, prepared using K from Preparation #Y.1 and cyclopropanesulfonyl chloride) in THF (14.5 mL) was cooled to about −78° C. and then LDA (1.8 M in THF/hexane, 3.63 mL, 6.53 mmol) was added dropwise to the reaction mixture over about 30 min. The reaction mixture was stirred at about −78° C. for about 50 min before a solution of N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (2.06 g, 6.53 mmol) in THF (7.3 mL) was added dropwise over about 30 min. The reaction mixture was stirred at about −78° C. for about 1 h and then was warmed to ambient temperature and stirred for about 16 h. Saturated aqueous NH4Cl (100 mL) was added. The reaction mixture was partitioned with EtOAc (50 mL). The aqueous layer was further extracted with EtOAc (2×50 mL). The combined organic layers were concd under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-60% EtOAc in heptane to yield ethyl 4-(cyclopropanesulfonamido)-2-ethyl-1-fluorocyclopentanecarboxylate (0.41 g, 46%) as clear oil: LC/MS (Table 1, Method b) Rt=2.12 min; MS m/z: 306 (M−H)−.

Workup

  1. additionwas added dropwise over about 30 min
  2. temperaturewas warmed to ambient temperature
  3. stirringstirred for about 16 h
  4. customThe reaction mixture was partitioned with EtOAc (50 mL)
  5. extractionThe aqueous layer was further extracted with EtOAc (2×50 mL)
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with a gradient of 0-60% EtOAc in heptane

Sources & evidence

ORD record
ord-34922c24e1294ee0bbcf97b20c159c83
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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