Tosylmethyl isocyanide → HCID 69736016, compound

HRID 497427Notes

Reaction equation

HRID 497427 reaction equation
S([CH2:11][N+:12]#[C-:13])(C1C=CC(C)=CC=1)(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:24]([O:26][C:27](=[O:46])[CH:28]=[CH:29][C:30]1[C:35]([CH2:36][N:37]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH3:38])=[CH:34][CH:33]=[CH:32][N:31]=1)[CH3:25]>C1COCC1>[CH2:24]([O:26][C:27]([C:28]1[C:29]([C:30]2[C:35]([CH2:36][N:37]([CH2:39][C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH3:38])=[CH:34][CH:33]=[CH:32][N:31]=2)=[CH:13][NH:12][CH:11]=1)=[O:46])[CH3:25]

Participants

5

Reactant 3

HCID 161915Tosylmethyl isocyanideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 69736596HCID 69736596, compound

Product 1

HCID 69736016HCID 69736016, compoundYield 93.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2.3 g (11.6 mmol) of tosylmethyl isocyanide in 25 mL of anhydrous THF is cooled to −50° C. under a nitrogen atmosphere. To this solution is added dropwise 23 mL (11.6 mmol) of potassium bis(trimethylsilyl) amide (0.5M solution in toluene) keeping the temperature <−50° C. After addition is complete this mixture is stirred for a 0.5 hour. To this mixture a solution of 1.8 g (5.8 mmol) of 3-{3-[[benzyl-methyl-amino]-methyl]-pyridin-2-yl}-acrylic acid ethyl ester dissolved in 10 mL of anhydrous THF is added dropwise maintaining a temperature <−50° C. After addition is complete the reaction mixture is quenched with 10 mL of water and extracted with ethyl acetate. The organic extracts are dried (Na2SO4) and evaporated. The residue is redissolved in approximately 100 mL of ethyl acetate and 100 mL of water. The pH of the mixture is adjusted to 2.0 with 1N HCL. The ethyl acetate layer is separated from the water layer. An additional 100 mL of ethyl acetate is added to the water layer and the pH adjusted to 9.0 with 1N NaOH. The ethyl acetate layer is separated from the water layer, dried (Na2SO4) and evaporated to yield 1.9 grams of 4-{3-[[benzyl-methyl-amino]-methyl]-pyridin-2-yl}-1H-pyrrole-3-carboxylic acid ethyl ester. 1H NMR (CDCl3) δ 8.5 (m, 1H), 8.0 (m, 1H), 7.35 (s, 6H), 7.30 (m, 5H), 7.20 (m, 1H), 6.60 (s, 1H), 4.0 (q, 2H), 3.42 (s, 2H), 3.38 (s, 2H), 2.0 (s, 3H), 1.0 (t, 3H). Mass spectrum: m/e=350.3 (p+1). TLC (10/1 chloroform/methanol) Rf=0.35. Step 9:

Workup

  1. customthe temperature <−50° C
  2. additionAfter addition
  3. additionis added dropwise
  4. temperaturemaintaining a temperature <−50° C
  5. additionAfter addition
  6. customis quenched with 10 mL of water
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic extracts are dried (Na2SO4)
  9. customevaporated
  10. dissolutionThe residue is redissolved in approximately 100 mL of ethyl acetate
  11. customThe ethyl acetate layer is separated from the water layer
  12. additionAn additional 100 mL of ethyl acetate is added to the water layer
  13. customThe ethyl acetate layer is separated from the water layer
  14. dry with materialdried (Na2SO4)
  15. customevaporated

Sources & evidence

ORD record
ord-cf63edc28e6247fbbe4c7d07cfc18f0a
Source dataset
uspto-grants-2005_09
Patent number
US06949562B2

Reaction notes

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