Sodium Hydroxide → HCID 68811973, compound

HRID 1766530Notes

Reaction equation

HRID 1766530 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 68811973HCID 68811973, compoundYield 12.3%

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). 111.1 g (725 mmol) racemic α-(acetyloxy)-α-methyl-cyclopropaneacetonitrile was emulsified in 6.0 L of 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 6.0 g of cholesterase from Candida cylindraceae (Roche Applied Sciences; Cat. No. 10129046) and the pH maintained at 7.0 by the controlled addition of 1.0 N sodium hydroxide solution under vigorous stirring. After a consumption of 618.3 mL solution (corresponding to 85% conversion) the reaction was stopped by adding 5 L dichloromethane under vigorous stirring. The emulsion was allowed to stand for phase separation. The organic phase was removed (the turbid part was filtered through silicon-treated Phase Separator (1PS; Whatman) and the filtrate stirred with ca. 1 L of Speedex filter aid). The aqueous phase was extracted again with 2×5 L dichloromethane. The combined organic phases were concentrated in vacuo down to a volume of ca. 40 mL and distilled (finally ca. 69–70° C./4 mbar) to give 13.70 g (89 mmol; 12%) of (S)-α-(acetyloxy)-α-methyl-cyclopropaneacetonitrile as a colorless oil. Analysis: >99% GC; 96.8% 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: −31.61° (c=1.00; EtOH); EI-MS: 154.1 (M+H+).

Workup

  1. customthe hydrolytic reaction
  2. additionby adding 6.0 g of cholesterase from Candida cylindraceae (Roche Applied Sciences
  3. customAfter a consumption of 618.3 mL solution (corresponding to 85% conversion) the reaction
  4. additionby adding 5 L dichloromethane under vigorous stirring
  5. customto stand for phase separation
  6. customThe organic phase was removed (the turbid part
  7. filtrationwas filtered through silicon-
  8. additiontreated Phase Separator (1PS; Whatman)
  9. stirringthe filtrate stirred with ca. 1 L of Speedex
  10. filtrationfilter aid)
  11. extractionThe aqueous phase was extracted again with 2×5 L dichloromethane
  12. concentrationThe combined organic phases were concentrated in vacuo down to a volume of ca. 40 mL
  13. distillationdistilled (finally ca. 69–70° C./4 mbar)

Sources & evidence

ORD record
ord-feeb3f2ccee647b9abc7eb7e94849491
Source dataset
uspto-grants-2007_06
Patent number
US07229999B2

Reaction notes

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