Potassium Carbonate → 3-(4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acid

HRID 534173

Reaktionsgleichung

Reaktionsgleichung von HRID 534173
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(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][C:33]([O:35]C(C)(C)C)=[O:34]>C(#N)C>[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]([CH2:31][CH2:32][C:33]([OH:35])=[O:34])[CH2:11][CH2:12]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 256128tert-Butyl 3-bromopropionateHCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

Produkt 1

HCID 665711263-(4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acidAusbeute 38,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (300 mg, 0.919 mmol) in acetonitrile (10 mL) was added potassium carbonate (381 mg, 2.76 mmol) followed by tert-butyl 3-bromopropanoate (211 mg, 1.011 mmol) was heated in a seal tube at 80° C. for 4 hours. The reaction mixture was filtered, and the filtrate evaporated to dryness. The resulting oil was dissolved in 2 ml of EtOH and 2 ml of 1 M NaOH. The reaction mixture was stirred for 20 min. The solution injected on a preperatory HPLC (2 to 10% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected. To each fraction was added 0.1 ml of 6 M HCl, and the fractions were evaporated to dryness. Acid was formed by deprotection of t-butyl during evaporation. 3-(4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acid (140 mg, 0.354 mmol, 38.5% yield) was isolated as yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ 7.29-7.37 (m, 2H), 7.11-7.29 (m, 3H), 3.65 (br. s., 2H), 3.45 (t, J=7.07 Hz, 2H), 3.23 (d, J=5.81 Hz, 2H), 3.11 (br. s., 2H), 3.04 (dt, J=4.01, 7.89 Hz, 1H), 2.90 (t, J=7.07 Hz, 2H), 2.62 (ddd, J=3.54, 6.63, 10.29 Hz, 1H), 2.04-2.29 (m, 3H), 1.70 (dd, 2H), 1.62 (ddd, J=4.42, 6.51, 10.55 Hz, 1H), 1.42 (q, J=6.91 Hz, 1H); LC-MS Rt=0.42 min; MS (ESI): 303.3 [M+H]+.

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. customthe filtrate evaporated to dryness
  3. dissolutionThe resulting oil was dissolved in 2 ml of EtOH
  4. customThe fractions were collected
  5. additionTo each fraction was added 0.1 ml of 6 M HCl
  6. customthe fractions were evaporated to dryness
  7. customAcid was formed by deprotection of t-butyl during evaporation

Quellen und Nachweise

ORD-Eintrag
ord-752d3a5a703f419e800b8fa9f7696e42
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853408B2

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