Hydrochloric Acid → (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

HRID 1609107Notes

Reaction equation

HRID 1609107 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([OH:19])=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.C[C@H](NC)[C@@H](O)C1C=CC=CC=1.O.Cl>C(OCC)(=O)C.CO>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([C:17]([OH:19])=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 7028PseudoephedrineHCID 196986472-Chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

Product 1

HCID 67637562(9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acidYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
25 °C

Procedure

To a solution of racemic 2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (100 g; 0.37M) in ethyl acetate (1.5L) and methanol (75mL) was added solid (1S,2S)-(+)-pseudoephedrine (61.1 g; 0.37M). With efficient agitation the mixture was warmed to reflux, held for 30 minutes and slowly cooled to 25° C. After a minimum of 2 h the slurry was filtered and washed with ethyl acetate to yield enriched diastereomeric salt (88.6 g; 0.20M; 55%; diastereomeric ratio 80:20, as determined by HPLC). The enriched salt was slurried in 3% methanolic ethyl acetate (2.74 L),warmed to reflux,held 30 minutes,cooled to 25 C. slowly, held 2 h and then filtered and washed with ethyl acetate to provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC). Treatment of the further enriched salt with 5% methanolic ethyl acetate using the same procedure yielded highly enriched salt (60.0 g; 0.14M; 85%; diastereomeric ratio 99:1, as determined by HPLC). This salt (60 g; 0.14M) was added to water (1L) and the consequent suspension acidified to pH 2-3 with concentrated hydrochloric acid (15 mL) and then extracted with diethyl ether (3×500 mL). The combined organic extracts were washed with brine,dried (MgSO4) and evaporated to an oil. Hexane was added and evaporated to afford enantiomerically enriched acid (36 g; 0.13M; 98% recovery; enantiomeric ratio 99:1, as determined by HPLC) as a white solid. Crystallisation from a mixture of hexane (360 mL) and cyclohexane (720 mL) afforded enantiomerically pure (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracene-carboxylic acid as a white solid (30 g, 0.11 mol, 81%) mp 172°-173° C. αD =+101° (c=2.0,CHCl3).

Workup

  1. temperatureWith efficient agitation the mixture was warmed
  2. temperatureto reflux
  3. filtrationAfter a minimum of 2 h the slurry was filtered
  4. washwashed with ethyl acetate
  5. customto yield
  6. waitto reflux,held 30 minutes
  7. temperaturecooled to 25 C
  8. waitslowly, held 2 h
  9. filtrationfiltered
  10. washwashed with ethyl acetate
  11. customto provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC)
  12. extractionextracted with diethyl ether (3×500 mL)
  13. washThe combined organic extracts were washed with brine,dried (MgSO4)
  14. customevaporated to an oil
  15. additionHexane was added
  16. customevaporated
  17. customto afford enantiomerically enriched acid (36 g; 0.13M; 98% recovery; enantiomeric ratio 99:1, as determined by HPLC) as a white solid
  18. customCrystallisation
  19. additionfrom a mixture of hexane (360 mL) and cyclohexane (720 mL)

Sources & evidence

ORD record
ord-cc34667ffc7a4fbaaa2c9de19124b99c
Source dataset
uspto-grants-1995_03
Patent number
US05399568

Reaction notes

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