Sodium hydride → (1R,2S)-1-cyano-2-hexyl-1-(4-methoxyphenyl)cyclopropane

HRID 973513Notes

Reaction equation

HRID 973513 reaction equation
[H-].[Na+].C1(C)C=CC(S(O[C@H:13]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:14][C@@H:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:16]#[N:17])(=O)=O)=CC=1.C([C@@]1(C2C=CC(OC)=CC=2)C[C@@H]1CCCCCC)#N>CN(C=O)C>[C:16]([C@:15]1([C:18]2[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)[CH2:14][C@@H:13]1[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])#[N:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 15733980(2S,4R)-4-p-toluenesulfonyloxy-2-(4-methoxyphenyl)-decanenitrileHCID 15733982(1S,2S)-1-cyano-2-hexyl-1-(4-methoxyphenyl)cyclopropane

Product 1

HCID 15733981(1R,2S)-1-cyano-2-hexyl-1-(4-methoxyphenyl)cyclopropaneYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a dispersion of 18 mg (0.75 mmol) of sodium hydride in 10 ml of DMF was added, with cooling with ice, a solution of 300 mg (0.70 mmol) of (2S,4R)-4-p-toluenesulfonyloxy-2-(4-methoxyphenyl)-decanenitrile in 10 ml of DMF. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was neutralized by adjusting the pH thereof to 7 with diluted hydrochloric acid, and then subjected to extraction with 250 ml of ether. The resulting ether solution was washed with water, dried with anhydrous magnesium sulfate, and then concentrated. The isomers in the residue were separated by silica gel column chromatography (Kieselgel 60, hexane/ethyl acetate=9/1) and then further separated and purified by high-pressure liquid chromatography for separation (Tosoh Corporation, Japan; Silica-60, 21.5 mmID×300 mm, hexane/ethanol=100/1). Thus, 163 mg (yield 90%, optical purity 94% ee) of a nonpolar product, (1R,2S)-1-cyano-2-hexyl-1-(4-methoxyphenyl)cyclopropane and 7 mg (yield 4%) of a polar product, (1S,2S)-1-cyano-2-hexyl-1-(4-methoxyphenyl)cyclopropane, were obtained.

Workup

  1. temperaturewith cooling with ice
  2. extractionto 7 with diluted hydrochloric acid, and then subjected to extraction with 250 ml of ether
  3. washThe resulting ether solution was washed with water
  4. dry with materialdried with anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customThe isomers in the residue were separated by silica gel column chromatography (Kieselgel 60, hexane/ethyl acetate=9/1)
  7. customfurther separated
  8. custompurified by high-pressure liquid chromatography for separation (Tosoh Corporation, Japan; Silica-60, 21.5 mmID×300 mm, hexane/ethanol=100/1)

Sources & evidence

ORD record
ord-f6578e72d1614c24bf28f027c5816411
Source dataset
uspto-grants-1991_11
Patent number
US05064564

Reaction notes

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