NADP nicotinamide-adenine-dinucleotide phosphate → Ethyl (3S)-4-chloro-3-hydroxybutanoate

HRID 1157110Notes

Reaction equation

HRID 1157110 reaction equation
O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.C1C=[N+]([C@@H]2O[C@H](COP(OP(OC[C@H]3O[C@@H](N4C5N=CN=C(N)C=5N=C4)[C@H](OP(O)(O)=O)[C@@H]3O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=C(C(N)=O)C=1.[Cl:61][CH2:62][C:63](=[O:70])[CH2:64][C:65]([O:67][CH2:68][CH3:69])=[O:66].[OH-].[Na+]>O.C(OCCCC)(=O)C>[Cl:61][CH2:62][C@@H:63]([OH:70])[CH2:64][C:65]([O:67][CH2:68][CH3:69])=[O:66]

Participants

7

Reactant 4

HCID 5886NADP nicotinamide-adenine-dinucleotide phosphateHCID 14798Sodium HydroxideHCID 69484Ethyl 4-chloroacetoacetateHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal

Product 1

HCID 7019277Ethyl (3S)-4-chloro-3-hydroxybutanoateYield 87.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31272Butyl AcetateSolvent

Procedure

To a 100 mL vessel connected to an automatic titrater by a pH electrode and a feeding tube for addition of base was charged a solution of glucose (12. g) in water (30 mL). To this solution was charged ketoreductase SEQ ID NO: 42 (100 mg); 50 mg GDH SEQ ID NO: 66 and NADP (6.25 mg). Butyl acetate (10 ml) was then charged. Ethyl 4-chloroacetoacetate (10 g) was then charged via syringe pump as follows: 1 mL was charged rapidly and the remainder was then charged at a rate of 1 mL/hr). The pH was maintained at 7 by the automatic titrater by the addition of 4M NaOH over 18 hours hrs. The stirring was stopped and the phases allowed to separate. The organic layer included some emulsion. The organic layer, including some emulsion, was separated and washed with 10 mL of water. The combined aqueous layers were extracted twice with 20 mL of butyl acetate. The organic extracts were combined and rotary evaporated under vacuum to remove water. Additional butyl acetate was added during the evaporation to help remove the water. When the water was removed the butyl acetate solution was decanted from solids in the flask. Evaporation of the solvent under vacuum then gave 8.85 g of ethyl (S)-4-chloro-3-hydroxybutyrate (87.4% yield) of very good purity.

Workup

  1. additionTo a 100 mL vessel connected to an automatic titrater by a pH electrode and a feeding tube for addition of base
  2. additionTo this solution was charged ketoreductase SEQ ID NO
  3. addition1 mL was charged rapidly
  4. additionthe remainder was then charged at a rate of 1 mL/hr)
  5. customto separate
  6. customwas separated
  7. washwashed with 10 mL of water
  8. extractionThe combined aqueous layers were extracted twice with 20 mL of butyl acetate
  9. customrotary evaporated under vacuum
  10. customto remove water
  11. additionAdditional butyl acetate was added during the evaporation
  12. customto help remove the water
  13. customWhen the water was removed the butyl acetate solution
  14. customwas decanted from solids in the flask
  15. customEvaporation of the solvent under vacuum

Sources & evidence

ORD record
ord-bb53a86410544e6baecdb101db1d438d
Source dataset
uspto-grants-2010_10
Patent number
US07807423B2

Reaction notes

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