Lithium Hydroxide → (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid

HRID 2261423Notes

Reaction equation

HRID 2261423 reaction equation
[Na].C([O:4][C:5](=[O:8])[CH2:6][SH:7])C.Cl/[C:10](=[C:12]1\[C@H:13]2[C@@H:15]([CH2:16][C:17]\1=O)[C:14]2([CH3:20])[CH3:19])/[CH3:11].[Li+].[OH-]>C(O)C>[CH3:19][C:14]1([CH3:20])[C@@H:15]2[CH2:16][C:17]3[C:12]([C@H:13]12)=[C:10]([CH3:11])[S:7][C:6]=3[C:5]([OH:4])=[O:8]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 12185Ethyl ThioglycolateHCID 5360545Sodium2×HCID 10702657(1S,5R)-2-(1-chloro-(E)-ethylidene)-6,6-dimethyl-bicyclo[3.1.0]hexan-3-one

Product 1

HCID 57892448(1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acidYield 66.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent4×

Conditions

Temperature
30 °C

Procedure

Alternatively, (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid is also obtained by the following procedure: To a solution of sodium (2.80 g, 122 mmol) in ethanol (400 mL) a solution of mercaptoacetic acid ethyl ester (14.64 g, 122 mmol) in ethanol (40 mL) is added. The solution is stirred for 5 min before (1S,5R)-2-(1-chloro-(E)-ethylidene)-6,6-dimethyl-bicyclo[3.1.0]hexan-3-one (15.0 g, 81.2 mmol) in ethanol (40 mL) is added dropwise. The solution becomes slightly warm (approx. 30° C.) and turns orange to brown. A fine precipitate forms. Stirring is continued at rt for 1 h. Then, a solution of sodium (2.24 g, 97.5 mmol) in ethanol (75 mL) is added rapidly and the mixture is heated to 75° C. for 1 h. A 2N aq. solution of LiOH (75 mL) is added and stirring is continued at 75° C. for 2h, then at rt for 16 h. About ⅔ of the solvent is removed in vacuo, the remaining mixture is diluted with water (250 mL) and extracted with DCM (200 mL). The organic extract is washed twice with 1 N aq. (100 mL). The combined aqueous layers are acidified by adding 2N aq. HCl and extracted three times with diethyl ether (3×300 mL). The organic extracts are dried over MgSO4 and evaporated. The remaining residue is suspended in acetonitrile, filtered, washed with additional acetonitrile and dried under high vacuum to give the title compound (12.02 g) as a pale yellow to beige crystalline powder.

Workup

  1. additionis added dropwise
  2. temperaturethe mixture is heated to 75° C. for 1 h
  3. stirringstirring
  4. waitat rt for 16 h
  5. customAbout ⅔ of the solvent is removed in vacuo
  6. additionthe remaining mixture is diluted with water (250 mL)
  7. extractionextracted with DCM (200 mL)
  8. extractionThe organic extract
  9. washis washed twice with 1 N aq. (100 mL)
  10. additionby adding 2N aq. HCl
  11. extractionextracted three times with diethyl ether (3×300 mL)
  12. dry with materialThe organic extracts are dried over MgSO4
  13. customevaporated
  14. filtrationfiltered
  15. washwashed with additional acetonitrile
  16. customdried under high vacuum

Sources & evidence

ORD record
ord-b530ff88b89a4f5dbd8d80ad1145e2b2
Source dataset
uspto-grants-2010_12
Patent number
US07846964B2

Reaction notes

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