Acetic Acid → (R)-5-aminomethyl-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride

HRID 854700Notes

Reaction equation

HRID 854700 reaction equation
[ClH:1].[F:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([F:13])[CH:12]=1)[O:9][CH2:8][C@H:7]([NH2:14])[CH2:6]2.C(OC(=O)[NH:21][CH2:22][C:23](=O)[CH2:24]O[Si](C(C)(C)C)(C)C)(C)(C)C.[S-:35][C:36]#[N:37].[K+].C(O)(=O)C>C(OCC)(=O)C>[ClH:1].[NH2:21][CH2:22][C:23]1[N:14]([C@@H:7]2[CH2:6][C:5]3[C:10](=[C:11]([F:13])[CH:12]=[C:3]([F:2])[CH:4]=3)[O:9][CH2:8]2)[C:36](=[S:35])[NH:37][CH:24]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 516872Potassium thiocyanateHCID 11615490(R)-6,8-difluorochroman-3-ylamine hydrochlorideHCID 11709260tert-Butyl (3-((tert-butyldimethylsilyl)oxy)-2-oxopropyl)carbamate

Product 1

HCID 11695681(R)-5-aminomethyl-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A stirred mixture of (R)-6,8-difluorochroman-3-ylamine hydrochloride (0.22 g, 1.0 mmol), [3-(tert-butyldimethylsilanyloxy)-2-oxopropyl]carbamic acid tert-butyl ester (0.33 g, 1.1 mmol), potassium thiocyanate (0.11 g, 1.1 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 2 hours, cooled to room temperature, then washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by the column chromatography over silica gel using ethyl acetate—petroleum ether mixture as eluent. The resulting oil (0.23 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HCl solution in ethyl acetate was added (2 mL, 4 mmol) and the mixture was stirred for 2 hours at room temperature. The precipitate was removed by filtration and washed with ethyl acetate to give crystals of m.p. 192° C. (decomp.).

Workup

  1. temperaturewas refluxed for 2 hours
  2. washwashed by sodium bicarbonate solution
  3. dry with materialdried over anhydrous magnesium sulphate
  4. customevaporated in vacuo
  5. customThe residue was purified by the column chromatography over silica gel
  6. dissolutionThe resulting oil (0.23 g) was dissolved in ethyl acetate (2 ml), whereupon 2M HCl solution in ethyl acetate
  7. additionwas added (2 mL, 4 mmol)
  8. customThe precipitate was removed by filtration
  9. washwashed with ethyl acetate
  10. customto give crystals of m.p. 192° C. (decomp.)

Sources & evidence

ORD record
ord-a32d9e5e9645405d8259c3c01d3265f0
Source dataset
uspto-grants-2007_08
Patent number
US07259271B2

Reaction notes

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