Sodium Chloride → Ethyl (3S)-4-chloro-3-hydroxybutanoate

HRID 719071Notes

Reaction equation

HRID 719071 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Na+].[Cl-].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:71][CH2:72][C:73](=[O:80])[CH2:74][C:75]([O:77][CH2:78][CH3:79])=[O:76].C([O-])([O-])=O.[Na+].[Na+]>C(OCCCC)(=O)C>[Cl:71][CH2:72][C@@H:73]([OH:80])[CH2:74][C:75]([O:77][CH2:78][CH3:79])=[O:76]

Participants

8

Reactant 6

HCID 5234Sodium ChlorideHCID 5886NADP nicotinamide-adenine-dinucleotide phosphateHCID 10340Sodium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 69484Ethyl 4-chloroacetoacetateHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal3×

Product 1

HCID 7019277Ethyl (3S)-4-chloro-3-hydroxybutanoateYield 97%

Reagents, catalysts & solvents 1

HCID 31272Butyl AcetateSolvent2×

Procedure

To a well-stirred solution of 100 mM potassium phosphate buffer, 500 mM NaCl, pH 7 (1 L) at room temperature was added glucose (160 g, 830 mmoles, 1.1 equiv). To this was added ketoreductase SEQ ID NO: 2 (0.9 g), glucose dehydrogenase S06 SEQ ID. NO: 10 (0.5 g) and NADP (0.5 g) as lyophilized powders. Once dissolved, butyl acetate (500 mL) was added to form an emulsion. To this emulsion was added a solution of ethyl 4-chloroacetoacetate (100 g, 608 mmoles) in butyl acetate (500 mL), dropwise over 3 hours. The pH was maintained between 6.8 and 7 by an automatic titrater that dispensed Na2CO3 (2M in water, about 160 mL total). After 40 hours the automated addition of the base had ceased and there was no residual starting material by gas chromatography. The layers were separated, and the aqueous phase was washed with ethyl acetate (500 mL). The combined organics were dried over anhydrous sodium sulfate, filtered and evaporated on a rotary evaporator, to give essentially pure (˜97%) ethyl (S)-4-chloro-3-hydroxybutyrate.

Workup

  1. additionTo this was added ketoreductase SEQ ID NO
  2. dissolutionOnce dissolved
  3. customto form an emulsion
  4. temperatureThe pH was maintained between 6.8 and 7 by an automatic titrater that
  5. additionAfter 40 hours the automated addition of the base
  6. customThe layers were separated
  7. washthe aqueous phase was washed with ethyl acetate (500 mL)
  8. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated on a rotary evaporator

Sources & evidence

ORD record
ord-a16bd48e0f614728896460969bee8c95
Source dataset
uspto-grants-2006_11
Patent number
US07132267B2

Reaction notes

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