Ethyl Acetate → 2-(4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethanol

HRID 534148Notes

Reaction equation

HRID 534148 reaction equation
FC(F)(F)C([N:5]([CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][OH:24])[CH2:18][CH2:17]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=O.[OH-].[Na+].C(OCC)(=O)C>C(O)C>[C:9]1([C@@H:7]2[CH2:8][C@H:6]2[NH:5][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][OH:24])[CH2:18][CH2:17]2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 867082362,2,2-Trifluoro-N-((1-(2-hydroxyethyl)piperidin-4-yl)methyl)-N-(trans-2-phenylcyclopropyl)acetamide

Product 1

HCID 665715832-(4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethanolYield 32.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To the solution of 2,2,2-trifluoro-N-((1-(2-hydroxyethyl)piperidin-4-yl)methyl)-N-(trans-2-phenylcyclopropyl)acetamide (40 mg, 0.108 mmol) in ethanol (2 mL) was added 1 M NaOH (1 mL, 1.000 mmol). The reaction was heated to 80° C. for 1 hr. Then 10 ml of ethyl acetate was added. Layers were separated, organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The oil was purified on preparative HPLC (5 to 70% AcCN: H2O gradient with 0.1% formic acid modifier). The fractions were collected. The combined fractions were neutralized with aq. NH4OH, concentrated and extracted with ethyl acetate. Organic layer was washed with brine, dried over MgSO4 and evaporated. 2-(4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethanol (10 mg, 0.035 mmol, 32.1% yield) was isolated as colorless oil. 1H NMR (400 MHz, METHANOL-d4) δ 7.19-7.28 (m, 2H), 7.10-7.16 (m, 1H), 7.03-7.09 (m, 2H), 3.70 (t, J=6.32 Hz, 2H), 2.95-3.08 (m, 2H), 2.61 (d, J=6.82 Hz, 2H), 2.54 (t, J=6.19 Hz, 2H), 2.25-2.37 (m, 1H), 2.02-2.16 (m, 2H), 1.92 (ddd, J=3.28, 5.87, 9.28 Hz, 1H), 1.69-1.85 (m, 2H), 1.49-1.64 (m, J=3.54, 7.48, 7.48, 14.84 Hz, 1H), 1.20-1.36 (m, 2H), 1.08 (dt, J=4.77, 9.41 Hz, 1H), 1.01 (dt, J=5.59, 7.26 Hz, 1H); LC-MS Rt=0.48 min; MS (ESI): 275.2 [M+H]+.

Workup

  1. customLayers were separated
  2. washorganic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe oil was purified on preparative HPLC (5 to 70% AcCN: H2O gradient with 0.1% formic acid modifier)
  7. customThe fractions were collected
  8. concentrationconcentrated
  9. extractionextracted with ethyl acetate
  10. washOrganic layer was washed with brine
  11. dry with materialdried over MgSO4
  12. customevaporated

Sources & evidence

ORD record
ord-c9654271531642d9a6dc671e6671e70c
Source dataset
uspto-grants-2014_10
Patent number
US08853408B2

Reaction notes

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