Methyl iodide → HCID 66571530, compound

HRID 529328Notes

Reaction equation

HRID 529328 reaction equation
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][CH:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].IC>C(#N)C.CN(C)C=O>[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 66571483HCID 66571483, compound

Product 1

HCID 66571530HCID 66571530, compoundYield 13.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl 4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxylate (100 mg, 0.303 mmol) in acetonitrile (2 ml) and N,N-dimethylformamide (DMF) (0.5 ml) was added potassium carbonate (125 mg, 0.908 mmol) followed by iodomethane (0.038 ml, 0.605 mmol). The reaction mixture was stirred for 4 hours at room temperature. The reaction mixture was evaporated. The oil was purified on preparatory HPLC (5 to 70% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected. The solution was neutralized with NH4OH, concentrated and extracted with ethyl acetate. The organic layer was dried and evaporated. The resulting oil was dissolved in 2 mL of dioxane and 1 mL of HCl. The reaction mixture was heated under reflux for 15 minutes then evaporated to dryness. 4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine (12 mg, 0.041 mmol, 13.41% yield) was isolated as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ 7.35 (d, J=4.29 Hz, 2H), 7.14-7.30 (m, 3H), 3.47 (d, J=13.14 Hz, 2H), 3.35-3.42 (m, 2H), 3.12-3.27 (m, 2H), 3.09 (d, J=8.34 Hz, 3H), 2.89-3.05 (m, 1H), 2.77-2.89 (m, 1H), 2.04-2.52 (m, 3H), 1.83 (d, J=5.56 Hz, 1H), 1.37-1.73 (m, 3H); LC-MS Rt=0.38 min; MS (ESI): 245.2 [M+H]+.

Workup

  1. customThe reaction mixture was evaporated
  2. customThe oil was purified on preparatory HPLC (5 to 70% AcCN: H2O with 0.1% formic acid modifier)
  3. customThe fractions were collected
  4. concentrationconcentrated
  5. extractionextracted with ethyl acetate
  6. customThe organic layer was dried
  7. customevaporated
  8. dissolutionThe resulting oil was dissolved in 2 mL of dioxane
  9. temperatureThe reaction mixture was heated
  10. temperatureunder reflux for 15 minutes
  11. customthen evaporated to dryness

Sources & evidence

ORD record
ord-e1d789c3043b4b2888758a3288c2a764
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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