Cyanomethyl ethanethioate → (1aS,5aR)-1,1,2-Trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carbonitrile

HRID 1821130Notes

Reaction equation

HRID 1821130 reaction equation
Cl/[C:2](=[C:4]1\[C@H:5]2[C@@H:7]([CH2:8][C:9]\1=O)[C:6]2([CH3:12])[CH3:11])/[CH3:3].[C:13]([CH2:15][S:16]C(=O)C)#[N:14]>C1COCC1.[OH-].[Na+]>[CH3:11][C:6]1([CH3:12])[C@@H:7]2[CH2:8][C:9]3[C:4]([C@H:5]12)=[C:2]([CH3:3])[S:16][C:15]=3[C:13]#[N:14]

Participants

5

Reactant 2

HCID 2777649Cyanomethyl ethanethioate2×HCID 10702657(1S,5R)-2-(1-chloro-(E)-ethylidene)-6,6-dimethyl-bicyclo[3.1.0]hexan-3-one

Product 1

HCID 57892441(1aS,5aR)-1,1,2-Trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carbonitrileYield 59.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent3×

Procedure

A solution of (1S, 5R)-2-(1-chloro-(E)-ethylidene)-6,6-dimethyl-bicyclo[3.1.0]hexan-3-one (997 mg, 5.40 mmol) and thioacetic acid S-cyanomethyl ester (746 mg, 6.48 mmol) in THF (37 mL) is treated with 2 N aq. NaOH (10.8 mL). The resulting mixture is stirred vigorously at rt for 2 h. Another portion of thioacetic acid S-cyanomethyl ester (100 mg, 0.87 mmol) and 2 N aq. NaOH (2 mL) is added and stirring is continued for 1 h. The reaction mixture is diluted with 2 N aq. NaOH and extracted twice with DCM. The organic extracts are dried over Na2SO4 and evaporated. The remaining brown oil is dissolved in THF (30 mL) and treated with 2 N aq. NaOH (3 mL). The mixture is heated to 90° C. for 4 h before it is diluted with 2 N aq. NaOH and extracted with DCM. The organic extracts are dried over Na2SO4 and evaporated. The crude product is purified by prep. HPLC (Phenomenex Aqua 30×75 mm, gradient 10 to 95% acetonitrile in water containing 0.5% formic acid) to give (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopro-pa[a]pentalene-4-carbonitrile (650 mg) as a brown oil; LC-MS: tR=1.06 min, [M+1+CH3CN]+=245.11; 1H NMR (CDCl3): δ 2.90 (dd, J=5.9, 18.8 Hz, 1H), 2.68 (d, J=18.8 Hz, 1H), 2.38 (s, 3H), 1.96-1.88 (m, 2H), 1.13 (s, 3H), 0.72 (s, 3H).

Workup

  1. stirringstirring
  2. waitis continued for 1 h
  3. extractionextracted twice with DCM
  4. dry with materialThe organic extracts are dried over Na2SO4
  5. customevaporated
  6. dissolutionThe remaining brown oil is dissolved in THF (30 mL)
  7. additiontreated with 2 N aq. NaOH (3 mL)
  8. temperatureThe mixture is heated to 90° C. for 4 h before it
  9. additionis diluted with 2 N aq. NaOH
  10. extractionextracted with DCM
  11. dry with materialThe organic extracts are dried over Na2SO4
  12. customevaporated
  13. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-59c374ba383241309a7f2c5fdc7c0503
Source dataset
uspto-grants-2009_10
Patent number
US07605269B2

Reaction notes

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