Hydrochloric Acid → (R)-N-(but-3-yn-2-yl)-2-chloro-5-fluoro-3-(trifluoromethyl)benzamide

HRID 2177652Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2177652
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1CC[C:17]2N(C3N=CC(F)=CN=3)N=N[C:16]=2[C@H:15]1[CH3:30])=[O:13].Cl.CCN(CC)CC.ClC1C(C(F)(F)[F:50])=CC=CC=1C(Cl)=O>C1COCC1>[CH3:30][C@@H:15]([NH:14][C:12](=[O:13])[C:3]1[CH:4]=[C:5]([F:50])[CH:6]=[C:7]([C:8]([F:11])([F:10])[F:9])[C:2]=1[Cl:1])[C:16]#[CH:17]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 38276332-Chloro-3-(trifluoromethyl)benzoyl chlorideHCID 90409366Jnj-54175446

Produkt 1

HCID 90409344(R)-N-(but-3-yn-2-yl)-2-chloro-5-fluoro-3-(trifluoromethyl)benzamideAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To the suspension of (R) but-3-yn-2-amine.HCl salt (10 g, 94.7 mmol, 1.0 equiv.) in THF (150 mL), Et3N (27.5 mL, 199 mmol, 2.1 equiv.) and (2-chloro-3-(trifluoromethyl)benzoyl chloride (23.1 g, 94.7 mmol, 1.0 equiv.) were added sequentially at 0° C. The reaction mixture was then stirred at room temperature for 16 hours. The precipitate was filtered off and washed with THF. The filtrate solution was concentrated and re-dissolved in EtOAc. The EtOAc solution was washed with saturated NaHCO3 and brine, dried over Na2SO4, concentrated. Trituration of the crude product from EtOAc/hexanes afforded the title compound (23 g, 83.8 mmol, 88%) as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.82-7.75 (dd, J=7.9, 1.6 Hz, 1H), 7.73-7.66 (dd, J=7.7, 1.6 Hz, 1H), 7.48-7.41 (dd, J=8.2, 7.3 Hz, 1H), 6.35-6.02 (d, J=7.9 Hz, 1H), 5.09-4.90 (dqd, J=8.1, 6.9, 2.3 Hz, 1H), 2.47-2.20 (m, 1H), 1.58-1.54 (d, J=6.9 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 164.7, 137.9, 132.5, 129.4 (q, JC—F=31.5 Hz), 129.1, 129.0 (q, JC—F=5.2 Hz), 127.1, 122.5 (q, JC—F=273.4 Hz), 83.2, 71.2, 37.8, 22.1. HRMS-ESI (m/z): [M+H]+ calcd for C12H10ClF3NO, 276.0398. found, 276.0390.

Aufarbeitung

  1. filtrationThe precipitate was filtered off
  2. washwashed with THF
  3. concentrationThe filtrate solution was concentrated
  4. dissolutionre-dissolved in EtOAc
  5. washThe EtOAc solution was washed with saturated NaHCO3 and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-a6c8777d0f5b4763a4048ebc6b7e47fb
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09066946B2

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