Hydrochloric Acid → Ethyl 3-(tert-butylsulfinylamino)-3-cyclopropyl-butanoate

HRID 1480323Notes

Reaction equation

HRID 1480323 reaction equation
Cl.Br[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH:9]1(/[C:12](=[N:14]/[S:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])/[CH3:13])[CH2:11][CH2:10]1>C1COCC1.[Zn].[Cu]Cl>[C:17]([S:15]([NH:14][C:12]([CH:9]1[CH2:11][CH2:10]1)([CH3:13])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:16])([CH3:18])([CH3:19])[CH3:20]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 7748Ethyl bromoacetateHCID 89421056(NE)-N-(1-cyclopropylethylidene)-2-methylpropane-2-sulfinamide

Product 1

HCID 90204431Ethyl 3-(tert-butylsulfinylamino)-3-cyclopropyl-butanoateYield 79%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 62652Cuprous chlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a flask containing zinc (Note: the zinc powder was activated by stirring 10 gr in 20 mL of 2.0M aqueous solution HCl (caution: strong exotherm occurs)) (3.49 g, 53.4 mmol) and copper (I) chloride (529 mg, 5.34 mmol) under a stream of argon was added dry THF (10.0 ml), the suspension was stirred at reflux for 30 minutes then the heating bath was removed. Slow addition of a solution of ethyl 2-bromoacetate (1.78 g, 10.7 mmol, Eq: 2.0) in dry THF (5.00 ml) (caution: reaction exothermic), when addition completed the suspension was stirred for 30 min at rt then 30 min at 50° C. The reaction was then cooled down to 0° C. and a solution of (E)-N-(1-cyclopropylethylidene)-2-methylpropane-2-sulfinamide (1 g, 5.34 mmol) in dry THF (5.00 ml) was added to the reaction. The reaction was then stirred at 0° C. and let to warm up to room temperature overnight. The reaction mixture was filtered through a pad of Celite and the filter pad was washed twice with ethyl acetate. The filtrate was washed with a 0.25M aqueous solution of citric acid, a 1M aqueous solution of sodium bicarbonate. The organic phase was dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography on silica eluting with a gradient of heptane/ethyl acetate to yield the title compound (1.16 g, 79%) as a yellow oil; MS (ESI, m/z): 276.3 (M+H+).

Workup

  1. temperatureat reflux for 30 minutes
  2. customthe heating bath was removed
  3. stirringwas stirred for 30 min at rt
  4. custom30 min
  5. customat 50° C
  6. stirringThe reaction was then stirred at 0° C.
  7. temperatureto warm up to room temperature overnight
  8. filtrationThe reaction mixture was filtered through a pad of Celite
  9. washthe filter pad was washed twice with ethyl acetate
  10. washThe filtrate was washed with a 0.25M aqueous solution of citric acid
  11. dry with materialThe organic phase was dried over sodium sulfate
  12. concentrationconcentrated in vacuo
  13. customThe crude material was purified by flash chromatography on silica eluting with a gradient of heptane/ethyl acetate

Sources & evidence

ORD record
ord-1448c87880c34d13a6d02f7d0ce19661
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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