Monobasic potassium phosphate → HCID 22921469, compound

HRID 2258418Notes

Reaction equation

HRID 2258418 reaction equation
OP([O-])(O)=O.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([C:23]#[N:24])([CH2:21][CH3:22])[CH2:15][CH2:16][C:17]([O:19]C)=[O:18])=[CH:10][CH:9]=1>[OH-].[Na+]>[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([C:23]#[N:24])([CH2:21][CH3:22])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 516951Monobasic potassium phosphateHCID 22921474HCID 22921474, compound

Product 1

HCID 22921469HCID 22921469, compoundYield 38.2%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
30 °C

Procedure

A 500 ml jacketed biotransformation vessel as charged with 0.1M KH2PO4, pH 7.0 (250 ml) and methyl 4-(4-aminophenyl)4-cyanohexanoate (5.0 g, 20.3 mmol). Candida cylindracea lipase (CCL; 5.0 g) was introduced and the mixture was agitated using an overhead stirrer. Temperature was maintained at 30° 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 10 ml of 1M NaOH had been added (equivalent to 50% conversion). This took about 3 hours. At this point, the biotransformation was quenched by the addition of NaCl (25 g) and the resulting mixture was extracted with diethyl ether (250 ml×4). The pH of the aqueous solution was then adjusted to 3 using conc. HCl and the mixture extracted with ethyl acetate (400 ml×3). The extracts were pooled, dried and concentrated under reduced pressure, yielding 1.8 g (38%) of 4-(4-aminophenyl)-4-cyanohexanoic acid, enriched in the (R)-enantiomer, in the form of a brown oil. Without further treatment, a sample of this material was reacted as described in Example 10.

Workup

  1. additionCandida cylindracea lipase (CCL; 5.0 g) was introduced
  2. additionhad been added (equivalent to 50% conversion)
  3. customThis took about 3 hours
  4. customAt this point, the biotransformation was quenched by the addition of NaCl (25 g)
  5. extractionthe resulting mixture was extracted with diethyl ether (250 ml×4)
  6. extractionthe mixture extracted with ethyl acetate (400 ml×3)
  7. customdried
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-924c0850a3a14d3791ed699de9fd74cc
Source dataset
uspto-grants-1997_08
Patent number
US05661014

Reaction notes

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