Hydrochloric Acid → (R)-6-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid

HRID 1899761Notes

Reaction equation

HRID 1899761 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([C:13]([O:15]C)=[O:14])[CH2:7][CH2:6]2.P([O-])([O-])([O-])=O.Cl.CC(=O)OCC(COC(=O)C)OC(=O)C.[OH-].[Na+]>C(O)(C)(C)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][C@H:8]([C:13]([OH:15])=[O:14])[CH2:7][CH2:6]2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1061PhosphateHCID 5541TriacetinHCID 14798Sodium HydroxideHCID 13058283Methyl 6-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate

Product 1

HCID 51358647(R)-6-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acidYield 41.4%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

3 g (0.0136 mol) of methyl 6-methoxy-1,2,3,4- tetrahydro-2-naphthoate are dissolved in 100 ml of tert-butanol, and 300 ml of phosphate buffer at pH 7 are added to the solution prepared in this way. The pH of the solution, which rises to 7.3-7.5, is lowered to 7.1 by the addition of 1 N HCl. 1.5 g of Sigma PPL enzyme (known as porcine pancreatic lipase type II, crude, Sigma L-3126 - 50 U/mg using triacetin) are added to the mixture. The pH tends to drop as the reaction progresses, but is kept constant by the addition of a 0.25 N solution of NaOH, the pH being controlled by an automatic titration apparatus. After 4-5 hours, when about 22 ml of 0.25 N NaOH have been consumed, sodium bicarbonate is added to the solution until the pH is 8 in order to stop the reaction by inactivation of the enzyme. Extraction is carried out with ethyl ether and the two phases are separated. The organic phase contains the unreacted ester principally of (S) configuration, which can be recovered as indicated in Example 2 below. The aqueous phase is acidified with concentrated sulfuric acid and the precipitate formed is filtered off to give 1.16 g of the title acid, which is crystallized from ethyl acetate. M.p. 130°-131° C.; [α]D20 =+57.8° (c=1.4%, CHCl3); ee 93.7% (HPLC performed under conditions (a)). This product is purer than that described in EP-A-436435, preparation (O) (i).

Workup

  1. customprepared in this way
  2. customto drop as the reaction progresses
  3. customwhen about 22 ml of 0.25 N NaOH have been consumed
  4. additionsodium bicarbonate is added to the solution until the pH is 8 in order
  5. customthe reaction by inactivation of the enzyme
  6. extractionExtraction
  7. customthe two phases are separated
  8. customcan be recovered
  9. customthe precipitate formed
  10. filtrationis filtered off

Sources & evidence

ORD record
ord-9fb836bde9c74270bb9a8316048cacf9
Source dataset
uspto-grants-1996_11
Patent number
US05573949

Reaction notes

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