Pivaloyl chloride → HCID 59318452, Verbindung

HRID 1021062Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1021062
[C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[C@@H:10]([CH3:14])[CH2:9]2)=[CH:3][CH:2]=1.C(OC(=O)[C@H](C)C[C@H:27]([N:41]1[C:45](=O)[CH2:44][CH2:43][C:42]1=O)CC1C=CC(C2C=CC=CC=2)=CC=1)C.C([Li])CCC.[C:55](Cl)(=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57]>C1COCC1>[C:1]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([C:55](=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57])[C:11](=[O:13])[C@@H:10]([CH3:14])[CH2:9]2)=[CH:5][CH:6]=1.[C:1]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([CH2:27][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)[C:11](=[O:13])[C@H:10]([CH3:14])[CH2:9]2)=[CH:5][CH:6]=1

Komponenten

7

Edukt 4

HCID 62493Pivaloyl chlorideHCID 59318451Sacubitril Impurity 3HCID 66739220Ethyl (2R,4S)-4-([1,1'-biphenyl]-4-ylmethyl)-2-methyl-4-(2,5-dioxopyrrolidin-1-yl)butanoateHCID 178418339Butyllithium

Produkt 2

HCID 59318452HCID 59318452, VerbindungHCID 68714094HCID 68714094, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

146 mg (3S,5S)-5-biphenyl-4-ylmethyl-3-methylpyrrolidin-2-one (2-b, R1=H) [9:1 diastereoisomer mixture [(2S,4S): (2R,4S)]] is added to 10 ml THF. The mixture is cooled to −78° C. and 381 μl butyllithium (1.59 M in hexane) are added. 81 μl Pivaloyl chloride is then added. After 4 h, the mixture is warmed to room temperature. The mixture is then quenched by the addition of saturated ammonium chloride solution and isopropyl acetate. The phases are separated and the organic phase dried (MgSO4) and then concentrated in vacuo. The residue is purified by column chromatography, by eluting with isopropyl acetate/hexane 3:1 to 1:0 to afford (3S,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one (2-b, R1=pivaloyl) and (3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one (2-a, R1=pivaloyl). Ratio of diastereoisomers determined by 1H NMR to be 4:1 [(3S,5S): (3R,5S)]. 1H NMR (CDCl3) for (2-b, R1=Piv): 1.09, 1.14 (3H), 1.30 (9H), 1.34 (1H), 2.01-2.66 (3H), 3.03, 3.27 (1H), 4.31, 4.50 (1H), 7.21-7.53 (9H). Diastereomeric ratio is determined by integration of the pairs of signals at [3.03 ppm (2-a, R1=Piv) and 3.27 ppm (2-b, R1=Piv)] or those at [4.31 ppm (2-b, R1=Piv) and 4.50 ppm (2-a, R1=Piv)] from the 1H NMR spectrum. Spectroscopic data for (2-a, R1=Piv) as in Example 5.

Aufarbeitung

  1. temperaturethe mixture is warmed to room temperature
  2. customThe mixture is then quenched by the addition of saturated ammonium chloride solution and isopropyl acetate
  3. customThe phases are separated
  4. dry with materialthe organic phase dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by column chromatography
  7. washby eluting with isopropyl acetate/hexane 3:1 to 1:0

Quellen und Nachweise

ORD-Eintrag
ord-44552940afd34324b8b5f02b39aceb1c
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716495B2

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