Triethylamine → HCID 66571302, compound

HRID 534177Notes

Reaction equation

HRID 534177 reaction equation
FC(F)(F)C([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O.C(N(CC)CC)C.Cl[C:32]([O:34][CH2:35][CH3:36])=[O:33]>C(Cl)(Cl)Cl>[C:16]1([C@@H:14]2[CH2:15][C@H:13]2[NH:5][CH2:6][CH:7]2[CH2:8][CH2:9][N:10]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:11][CH2:12]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

Product 1

HCID 66571302HCID 66571302, compoundYield 64.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (170 mg, 0.521 mmol) in chloroform (10 mL) was added triethylamine (0.145 mL, 1.042 mmol) followed by ethyl chloroformate (0.055 mL, 0.573 mmol). The reaction mixture was stirred for 1 hour at room temperature and then it was evaporated to dryness. The oil was partitioned between 3 mL of ethanol and 3 M of 1 M NaOH. After 1 hour, the reaction mixture was concentrated, and 10 mL of ethyl acetate followed by 4 mL of brine were added. The organic layer was separated, dried over MgSO4, filtered and evaporated. The resulting oil was dissolved in 5 mL of 10% AcCN:Et2O and 0.5 mL of 4 M HCl/dioxane was added. The suspension was stirred for 30 min, and then it was filtered. Ethyl 4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxylate (120 mg, 0.336 mmol, 64.6% yield) was isolated as white solid. 1H NMR (400 MHz, METHANOL-d4) δ 7.30-7.39 (m, 2H), 7.22-7.29 (m, 1H), 7.11-7.22 (m, 2H), 4.19 (dd, J=1.26, 13.64 Hz, 2H), 4.13 (q, J=7.16 Hz, 3H), 3.15 (d, J=7.07 Hz, 2H), 3.02 (dt, J=4.14, 7.64 Hz, 1H), 2.86 (d, J=3.28 Hz, 2H), 2.54 (ddd, J=3.66, 6.69, 10.36 Hz, 1H), 1.99 (ddd, J=4.04, 7.52, 11.18 Hz, 1H), 1.82 (d, J=12.13 Hz, 2H), 1.56 (ddd, J=4.29, 6.63, 10.55 Hz, 1H), 1.42 (q, J=6.82 Hz, 1H), 1.27 (t, J=7.07 Hz, 3H), 1.17-1.33 (m, 1H); LC-MS Rt=0.76 min; MS (ESI): 303.3 [M++H]+.

Workup

  1. customit was evaporated to dryness
  2. customThe oil was partitioned between 3 mL of ethanol and 3 M of 1 M NaOH
  3. waitAfter 1 hour
  4. concentrationthe reaction mixture was concentrated
  5. additionwere added
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe resulting oil was dissolved in 5 mL of 10% AcCN
  11. additionEt2O and 0.5 mL of 4 M HCl/dioxane was added
  12. stirringThe suspension was stirred for 30 min
  13. filtrationit was filtered

Sources & evidence

ORD record
ord-d42e37aa2a164b1ab09f68dd353b6ad7
Source dataset
uspto-grants-2014_10
Patent number
US08853408B2

Reaction notes

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