Sodium Hydroxide → HCID 54178952, compound

HRID 2258422Notes

Reaction equation

HRID 2258422 reaction equation
OP([O-])(O)=O.[K+].[C:7]([C:9]([C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1)([CH2:16][CH3:17])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])#[N:8].[OH-].[Na+]>>[C:7]([C@:9]([C:18]1[CH:19]=[CH:20][C:21]([N+:24]([O-:26])=[O:25])=[CH:22][CH:23]=1)([CH2:16][CH3:17])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])#[N:8]

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 516951Monobasic potassium phosphateHCID 22921473HCID 22921473, compound

Product 1

HCID 54178952HCID 54178952, compoundYield 50.3%

Conditions

Temperature
37 °C

Procedure

A 1 l jacketed biotransformation vessel was charged with 0.05M KH2PO4, pH 7.5 (500 ml) and methyl 4-cyano-4-(4-nitrophenyl)hexanoate (20 g, 72 mmol). α-Chymotrypsin (ex. Aldrich; 4 g) was introduced and the mixture was agitated using an overhead stirrer. Temperature was maintained at 37° C. with the aid of a thermocirculator and the pH controlled by a probe linked to an autotitrator. The biotransformation was allowed to proceed until 18 ml of 1M NaOH had been added (equivalent to 50% conversion). This took about 68 hours, with addition of more α-chymotrypsin (1 g portions) after 24 hours and 50 hours. At this point, the biotransformation was quenched by the addition of NaCl (50 g) and the resulting mixture was extracted with diethyl ether (500 ml×3). The extracts were pooled, dried and concentrated under reduced pressure, yielding 10 g (50%) of (R)-methyl 4-cyano-4-(4-nitrophenyl)hexanoate, enriched in the (R)-enantiomer, 70% ee by chiral HPLC analysis.

Workup

  1. additionα-Chymotrypsin (ex. Aldrich; 4 g) was introduced
  2. additionhad been added (equivalent to 50% conversion)
  3. additionThis took about 68 hours, with addition of more α-chymotrypsin (1 g portions) after 24 hours
  4. custom50 hours
  5. customAt this point, the biotransformation was quenched by the addition of NaCl (50 g)
  6. extractionthe resulting mixture was extracted with diethyl ether (500 ml×3)
  7. customdried
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-312eafd7995d4b81939983147437d165
Source dataset
uspto-grants-1997_08
Patent number
US05661014

Reaction notes

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