Water → HCID 178501124, compound

HRID 529330Notes

Reaction equation

HRID 529330 reaction equation
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]1)=O.C([BH3-])#N.[Na+].O>CO>[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][C@H:13]2[CH2:14][CH2:15][C@H:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:17][CH2:18]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 19493(1R,2S)-TranylcypromineHCID 5003444Sodium cyanoborohydrideHCID 178501146HCID 178501146, compound

Product 1

HCID 178501124HCID 178501124, compoundYield 41.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of trans-2-phenylcyclopropanamine (80 mg, 0.601 mmol) in methanol (10 mL) was added trans-methyl 4-formylcyclohexanecarboxylate (102 mg, 0.601 mmol) and the reaction was heated to reflux for 2 minutes. After cooling back to the room temperature, sodium cyanoborohydride (75 mg, 1.201 mmol) was added to the reaction mixture and was stirred for 1 hour. Water (20 mL) was added. The reaction was concentrated and 20 mL of ethyl acetate was added. The layers were separated. The organic layer was washed with water, brine, and dried over MgSO4, filtered and evaporated. The resulting oil was purified on preparatory HPLC (10 to 60% AcCN:water with 0.1% formic acid as modifier). 0.5 mL of 6 M HCl was added into each fraction and the product was evaporated. trans-Methyl 4-(((trans-2-phenylcyclopropyl)amino)methyl)cyclohexanecarboxylate (95 mg, 0.250 mmol, 41.7% yield) was isolated as white solid. 1H NMR (400 MHz, METHANOL-d4) δ 7.29-7.38 (m, 2H), 7.22-7.29 (m, 1H), 7.11-7.22 (m, 2H), 3.68 (s, 3H), 3.09 (d, J=7.07 Hz, 2H), 2.99 (dt, J=4.11, 7.45 Hz, 1H), 2.49 (ddd, J=3.79, 6.57, 10.36 Hz, 1H), 2.35 (tt, J=3.63, 12.28 Hz, 1H), 2.07 (dd, J=3.54, 13.39 Hz, 2H), 1.93 (dd, J=3.28, 13.14 Hz, 2H), 1.66-1.83 (m, J=3.57, 3.57, 7.70, 7.70, 15.36 Hz, 1H), 1.50-1.58 (m, 1H), 1.36-1.50 (m, 3H), 1.15 (qd, J=3.54, 12.72 Hz, 2H); LC-MS Rt=0.83 min; MS (ESI): 288.2 [M+H]+.

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 2 minutes
  3. additionwas added to the reaction mixture
  4. concentrationThe reaction was concentrated
  5. addition20 mL of ethyl acetate was added
  6. customThe layers were separated
  7. washThe organic layer was washed with water, brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe resulting oil was purified on preparatory HPLC (10 to 60% AcCN:water with 0.1% formic acid as modifier)
  12. addition0.5 mL of 6 M HCl was added into each fraction
  13. customthe product was evaporated

Sources & evidence

ORD record
ord-3cee3712f8014bf3b1ba6e2c67e2925f
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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