Trifluoroacetic acid → 2,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

HRID 529294Notes

Reaction equation

HRID 529294 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]([N:5]([CH2:15][CH:16]1[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[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:4].FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[F:30][C:2]([F:1])([F:29])[C:3]([N:5]([C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:15][CH:16]1[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]1)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86708235tert-butyl 4-((2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)acetamido)methyl)piperidine-1-carboxylate

Product 1

HCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideYield 80%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To the solution of tert-butyl 4-((2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)acetamido)methyl)piperidine-1-carboxylate (700 mg, 1.641 mmol) in chloroform (2 mL) was added trifluoroacetic acid (2 ml, 26.0 mmol). The reaction mixture was stirred at the room temperature for 1 hr. The reaction was evaporated, and then 2 ml of 1 M Na2CO3 (2 mL) were added followed by 10 mL of ethyl acetate. The organic layer was separated, washer with brine, dried over MgSO4, filtered and evaporated. 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (450 mg, 1.310 mmol, 80% yield) was isolated as yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.30-7.38 (m, 2H), 7.27 (d, J=7.33 Hz, 1.5H), 7.08 (d, J=7.33 Hz, 1.5H), 3.35-3.49 (m, 1.7H), 3.10-3.22 (m, 2H), 2.97-3.09 (m, 0.8H), 2.52-2.67 (m, 2H), 2.30-2.44 (m, 0.8H), 1.75-2.10 (m, 2.3H), 1.59-1.75 (m, 2.4H), 1.39-1.58 (m, 2H), 1.13-1.38 (m, 2.5H); LC-MS Rt=0.70 min; MS (ESI): 327.2 [M+H]+.

Workup

  1. customThe reaction was evaporated
  2. addition2 ml of 1 M Na2CO3 (2 mL) were added
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-a2b102f79dd44c45aa1aadcca8a2fccf
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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