Acetic Acid → 6-Methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid

HRID 1032260Notes

Reaction equation

HRID 1032260 reaction equation
C(C1(O[Si](C)(C)C)[C:12]2[C:7](=[CH:8][C:9]([O:13][CH3:14])=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4]1)#N.Cl.[C:21]([OH:24])(=[O:23])[CH3:22]>>[CH3:14][O:13][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[CH:22]([C:21]([OH:24])=[O:23])[CH2:4][CH2:5][CH2:6]2

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 1872796-Methoxy-1-trimethylsilyloxy-tetralin-1-carbonitrile

Product 1

HCID 127907946-Methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid

Procedure

As described with reference to Reaction Scheme I, compounds of Formula 2 can be converted to the intermediates of Formula 3 according to the procedure described by Belletire, et al. [Synthetic Commun., 12(10), 763-770 (1982)]. For example, to a 250 ml single neck round bottom reaction flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet, is added 6.0 g (21.79 mmol) of 1-cyano-1-trimethylsiloxy-6-methoxy-1,2,3,4-tetrahydronaphthalene. In one portion, 20.0 g (88.6 mmol) stannous chloride decahydrate followed by 20 ml glacial acetic acid and 20 ml concentrated hydrochloric acid is added. The reaction apparatus is immediately flushed with nitrogen and plunged into a preheated (140° C.) oil bath. With vigorous stirring the reaction mixture is heated at reflux for 65 hours, cooled to room temperature, diluted with 250 ml chloroform, the layers separated, and the aqueous layer again extracted with chloroform. The combined organic layers are extracted three times with 2N aqueous KOH, and the combined basic aqueous layers back-extracted with ether. The basic aqueous layer is acidified with ice-bath cooling, extracted three times with chloroform, the organic layers dried over magnesium sulfate, filtered, and the volatiles removed to give 6-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid, an intermediate of Formula 3, as a crystalline solid.

Workup

  1. temperaturereflux condenser and nitrogen inlet
  2. additionis added
  3. customThe reaction apparatus is immediately flushed with nitrogen
  4. customplunged into a preheated (140° C.) oil bath
  5. temperatureis heated
  6. temperatureat reflux for 65 hours
  7. additiondiluted with 250 ml chloroform
  8. customthe layers separated
  9. extractionthe aqueous layer again extracted with chloroform
  10. extractionThe combined organic layers are extracted three times with 2N aqueous KOH
  11. extractionthe combined basic aqueous layers back-extracted with ether
  12. customThe basic aqueous layer is acidified with ice-bath
  13. temperaturecooling
  14. extractionextracted three times with chloroform
  15. dry with materialthe organic layers dried over magnesium sulfate
  16. filtrationfiltered
  17. customthe volatiles removed

Sources & evidence

ORD record
ord-447de569c906493b91c7444f180dbd18
Source dataset
uspto-grants-1990_09
Patent number
US04957914

Reaction notes

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