Sulfuric Acid → HCID 54754810, compound

HRID 2406870Notes

Reaction equation

HRID 2406870 reaction equation
S(=O)(=O)(O)O.[CH2:6]=[C:7]1[C:13]2([CH2:17][CH2:16][CH2:15][CH2:14]2)[CH:11]2[CH2:12][CH:8]1[CH2:9][CH2:10]2.[S-][C:19]#[N:20].[K+].[H-].COCCO[Al+]OCCOC.[Na+].[H-].[OH-].[Na+]>C1(C)C=CC=CC=1.Cl[O-].[Na+]>[CH3:19][NH:20][C:7]1([CH3:6])[C:13]2([CH2:17][CH2:16][CH2:15][CH2:14]2)[CH:11]2[CH2:12][CH:8]1[CH2:9][CH2:10]2

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 516872Potassium thiocyanateHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 86691657HCID 86691657, compound

Product 1

HCID 54754810HCID 54754810, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 23665760Sodium HypochloriteSolvent

Conditions

Temperature
85 °C

Procedure

Sulfuric acid (1.61 mL, 2.96 g, 30.2 mmol) was slowly added to a suspension of 3-methylenespiro[bicyclo[2.2.1]heptane-2,1′-cyclopentane]. (4.80 g, 29.6 mmol) and potassium thiocyanate. (2.96 g, 30.2 mmol) at 50° C. The reaction mixture was then stirred at 85° C. for 5.5 h, cooled to ambient temperature, diluted with toluene (30 mL) and washed with water (20 mL) followed by with saturated aqueous sodium bicarbonate (10 mL). The toluene layer was dried over anhydrous sodium sulfate and filtered To the filtrate was added sodium bis(methoxyethoxy)aluminum hydride (40% solution in toluene, 2 equivalents) and the reaction was stirred at 85° C. for 2 h. The reaction was cooled to 0° C., and a solution of 3N aqueous sodium hydroxide (20 mL) in 5% aqueous sodium hypochlorite (35 mL) was slowly added (drop-wise at intervals). The toluene layer was separated and washed with water (30 mL). The toluene layer was then extracted with 1N aqueous hydrochloric acid (2×10 mL) and discarded. The aqueous hydrochloric acid layer was made basic (to pH 10) by addition of 10% aqueous sodium hydroxide and extracted with diethyl ether. The diethyl ether extracts were concentrated, and the residue was purified by silica gel column chromatography, using 0-40% CMA (chloroform:methanol:30% aqueous ammonia, 9:1:0.1) in chloroform to obtain N,3-dimethylspiro[bicyclo[2.2.1]heptane-2,1′-cyclopentan]-3-amine (1.2 g, 53%) as oil. 1H NMR (CDCl3, 400 MHz): δ 2.28 (s, 3H), 2.24 (bs, 1H), 1.84-1.76 (m, 2H), 1.73-1.68 (m, 1H), 1.62-1.52 (m, 4H), 1.48-1.24 (m, 7H), 1.09-1.05 (m, 1H), 1.04 (s, 3H); LCMS (m/z): 194 (M+1).

Workup

  1. customat 50° C
  2. temperaturecooled to ambient temperature
  3. washwashed with water (20 mL)
  4. dry with materialThe toluene layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered To the filtrate
  6. stirringthe reaction was stirred at 85° C. for 2 h
  7. temperatureThe reaction was cooled to 0° C.
  8. customThe toluene layer was separated
  9. washwashed with water (30 mL)
  10. extractionThe toluene layer was then extracted with 1N aqueous hydrochloric acid (2×10 mL)
  11. additionby addition of 10% aqueous sodium hydroxide
  12. extractionextracted with diethyl ether
  13. concentrationThe diethyl ether extracts were concentrated
  14. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ff304e6d6ba84c41b120e091cfaa2731
Source dataset
uspto-grants-2014_08
Patent number
US08809397B2

Reaction notes

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