Tetrahydrofuran → 6,7,8,9-Tetrahydro-5H-benzocycloheptene-7-carboxylic acid

HRID 1181398Notes

Reaction equation

HRID 1181398 reaction equation
[N+](CC1CC[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)([O-])=O.CC(C)([O-:19])C.[K+].[O-][Mn](=O)(=O)=O.[K+].OS([O-])=O.[Na+].[CH2:33]1[CH2:37][O:36][CH2:35][CH2:34]1>O.COC(C)(C)C>[CH:14]1[C:15]2[CH2:37][CH2:33][CH:34]([C:35]([OH:19])=[O:36])[CH2:6][CH2:7][C:8]=2[CH:9]=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 516875Potassium PermanganateHCID 23665647Potassium tert-butoxideHCID 23665763Sodium BisulfiteHCID 131726646HCID 131726646, compound

Product 1

HCID 591711056,7,8,9-Tetrahydro-5H-benzocycloheptene-7-carboxylic acidYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 7-(nitromethyl)-6,7,8,9-tetrahydro-5H-benzo[α][7]annulene (Description 27; 96 g, 0.47 mol) in THF (550 ml) was cooled to −18° C. and potassium tert-butoxide (1.6M in THF, 263 ml, 0.42 mol) was added dropwise over 30 minutes while maintaining the temperature between −15 and −5° C. After stirring for 10 minutes a solution of KMnO4 (111 g, 0.7 mol) in water (900 ml) was added dropwise over 75 minutes while maintaining the temperature between −3 and 3° C. The mixture was stirred at 0° C. until GC analysis indicated the reaction was complete. tert-Butyl methyl ether (500 ml) was added followed by saturated aqueous NaHSO3 (1000 ml) and the resulting mixture was stirred for 30 minutes until a milky white slurry formed. This slurry was filtered, washed with a solution of 3N NaOH (50 ml) and water (100 ml) followed by tert-butyl methyl ether (100 ml). The pH of the filtrate was adjusted from 8.6 to 12.5 by the addition of 3N NaOH (100 ml) and 6N NaOH (40 ml). The phases were separated and to the aqueous phase was added tert-butyl methyl ether (500 ml). The pH of the resulting mixture was adjusted to 2 with 6N HCl (200 ml). The phases were again separated and the aqueous phase was extracted with tert-butyl methyl ether (2×300 ml). The organic phases were combined, dried over MgSO4, filtered and evaporated to give the title compound (73 g, 89%), as an off white solid.

Workup

  1. temperaturewhile maintaining the temperature between −15 and −5° C
  2. additionwas added dropwise over 75 minutes
  3. temperaturewhile maintaining the temperature between −3 and 3° C
  4. stirringthe resulting mixture was stirred for 30 minutes until a milky white slurry
  5. customformed
  6. filtrationThis slurry was filtered
  7. washwashed with a solution of 3N NaOH (50 ml) and water (100 ml)
  8. additionThe pH of the filtrate was adjusted from 8.6 to 12.5 by the addition of 3N NaOH (100 ml) and 6N NaOH (40 ml)
  9. customThe phases were separated and to the aqueous phase
  10. additionwas added tert-butyl methyl ether (500 ml)
  11. customThe phases were again separated
  12. extractionthe aqueous phase was extracted with tert-butyl methyl ether (2×300 ml)
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. customevaporated

Sources & evidence

ORD record
ord-40a87ad7854c412fbda339d032ae19ae
Source dataset
uspto-grants-2007_10
Patent number
US07285563B2

Reaction notes

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