Lithium Hydroxide → HCID 57508882, compound

HRID 2240787Notes

Reaction equation

HRID 2240787 reaction equation
[Na].Cl[CH:3]=[C:4]1[CH2:9][C:8]([CH3:11])([CH3:10])[CH2:7][CH2:6][C:5]1=O.[Li+].[OH-].C([O:17][C:18](=[O:21])[CH2:19][SH:20])C>C(O)C.C1COCC1>[CH3:10][C:8]1([CH3:11])[CH2:7][CH2:6][C:5]2=[C:19]([C:18]([OH:21])=[O:17])[S:20][CH:3]=[C:4]2[CH2:9]1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 12185Ethyl ThioglycolateHCID 5360545Sodium2×HCID 67189348HCID 67189348, compound

Product 1

HCID 57508882HCID 57508882, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a part (300 mL) of a freshly prepared solution of sodium (21 g, 875 mmol) in ethanol (500 mL), mercaptoacetic acid ethyl ester (50 mL) is added. The resulting solution is added over a period of 10 min to a solution of 2-chloromethylene-4,4-dimethyl-cyclohexanone (50 g, 290 mmol) in THF (170 mL). The mixture becomes warm (50° C.). Upon complete addition, the remaining part of the freshly prepared solution of sodium in ethanol (200 mL) is added to the reaction mixture. The mixture is stirred at rt for 15 min before 1 N aq. LiOH solution (300 mL) is added. The solution is refluxed for 3 h, then stirred at rt for 16 h. The THF and ethanol are removed under reduced pressure and the remaining dark solution is extracted with heptane/EA 3:1 (2×200 mL). The aq. phase is acidified by adding citric acid (30 g) and 2 N aq. HCl (200 mL) and then extracted three times with EA. The combined organic extracts are washed three times with sat. aq. NaHCO3 solution, dried over Na2SO4 and evaporated. The resulting dark brown oil is dissolved in acetonitrile at 60° C. and crystallised at 5° C. The crystals are collected, washed with acetonitrile and dried to give 5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (31 g) as a slightly grey powder; LC-MS: tR=0.95 min, [M+1+CH3CN]+=252.18; 1H NMR (CDCl3): δ 7.15 (s, 1H), 3.05 (t, J=7.0 Hz, 2H), 2.47 (s, 2H), 1.58 (t, J=7.0 Hz, 2H), 0.97 (s, 6H).

Workup

  1. additionUpon complete addition
  2. additionis added
  3. temperatureThe solution is refluxed for 3 h
  4. customThe THF and ethanol are removed under reduced pressure
  5. extractionthe remaining dark solution is extracted with heptane/EA 3:1 (2×200 mL)
  6. additionby adding citric acid (30 g) and 2 N aq. HCl (200 mL)
  7. extractionextracted three times with EA
  8. washThe combined organic extracts are washed three times with sat. aq. NaHCO3 solution
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. dissolutionThe resulting dark brown oil is dissolved in acetonitrile at 60° C.
  12. customcrystallised at 5° C
  13. customThe crystals are collected
  14. washwashed with acetonitrile
  15. customdried

Sources & evidence

ORD record
ord-1d519f1c957d4de48fe7ed7651f70eac
Source dataset
uspto-grants-2010_05
Patent number
US07723378B2

Reaction notes

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