Sodium Hydroxide → HCID 67504647, compound

HRID 1766548Notes

Reaction equation

HRID 1766548 reaction equation
[C:1]([O:4][C:5]([CH3:11])([CH:8]1[CH2:10][CH2:9]1)[C:6]#[N:7])(=[O:3])[CH3:2].[OH-].[Na+]>[Cl-].[Na+]>[C:1]([O:4][C@:5]([CH3:11])([CH:8]1[CH2:10][CH2:9]1)[C:6]#[N:7])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 21109722α-(Acetyloxy)-α-methylcyclopropaneacetonitrile

Product 1

HCID 67504647HCID 67504647, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 5234Sodium ChlorideSolvent

Conditions

Temperature
10 °C

Procedure

(Warning: Highly toxic hydrogen cyanide is formed in the experiment; use adequate protection). 119.8 g (782 mmol) racemic α-(acetyloxy)-α-methyl-cyclopropaneacetonitrile was emulsified in 7.0 L 0.1 M sodium chloride/3.8 mM sodium phosphate buffer pH 7.0 by stirring. The emulsion was cooled to 10° C. and the hydrolytic reaction started by adding 8.0 g of triacylglycerol lipase from wheat germ (Sigma L-3001) and the pH maintained at 7.0 by the controlled addition of 1.0 N sodium hydroxide solution under vigorous stirring at 10° C. After a consumption of 605.8 mL solution (corresponding to 78% conversion), after 118 h, the reaction was stopped by adding 6 L dichloromethane under vigorous stirring. The emulsion was allowed to stand overnight for phase separation. The organic phase was removed (the turbid part was filtered through silicon-treated Phase Separator (1 PS; Whatman) and the filtrate stirred with ca. 1 L of Speedex filter aid). The aqueous phase was extracted again with 2×6 L dichloromethane. The combined organic phases were concentrated in vacuo down to a volume of ca. 40 mL and distilled (final temp. 68–69° C./4 mbar) to give 17.88 g (117 mmol; 15%) of (R)-α-(acetyloxy)-α-methyl-cyclopropaneacetonitrile as a colorless oil. Analysis: purity >99% GC; 98.0% ee (column: BGB-176; 30 m×0.25 mm; 100–140° C. with 2° C./min; H2; 90 kPa; Inj. 200° C.; Det. 210° C.); αD20:+32.92° (c=1.00; EtOH).

Workup

  1. customthe hydrolytic reaction
  2. stirringunder vigorous stirring at 10° C
  3. customAfter a consumption of 605.8 mL solution (corresponding to 78% conversion)
  4. additionby adding 6 L dichloromethane under vigorous stirring
  5. customto stand overnight for phase separation
  6. customThe organic phase was removed (the turbid part
  7. filtrationwas filtered through silicon-
  8. additiontreated Phase Separator (1 PS; Whatman)
  9. stirringthe filtrate stirred with ca. 1 L of Speedex
  10. filtrationfilter aid)
  11. extractionThe aqueous phase was extracted again with 2×6 L dichloromethane
  12. concentrationThe combined organic phases were concentrated in vacuo down to a volume of ca. 40 mL
  13. distillationdistilled (final temp

Sources & evidence

ORD record
ord-31b25749d8be47f6ad471355434653e3
Source dataset
uspto-grants-2007_06
Patent number
US07229999B2

Reaction notes

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