2-Chloromethyl 2-(trimethylsilyl)ethyl ether → (S)-5-Biphenyl-4-ylmethyl-1-(2-trimethylsilanylethoxymethyl)pyrrolidin-2-one

HRID 882534Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 882534
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.C([Li])CCC.Cl[CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31]>C1COCC1.CCCCCC>[C:1]1([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:5][CH:6]=1

Komponenten

6

Edukt 3

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58160438(S)-5-[(Biphenyl-4-yl)methyl]pyrrolidin-2-oneHCID 178418339Butyllithium

Produkt 1

HCID 59318461(S)-5-Biphenyl-4-ylmethyl-1-(2-trimethylsilanylethoxymethyl)pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

804 mg (3.2 mmol) (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) is dissolved in 16 ml dry THF and cooled to −78° C. After the addition of 2.21 ml butyl lithium in hexane (1.59 M), the yellow solution is stirred at −78° C. for 30 min. Subsequently, 680 l (640 mg=3.84 mmol) (2-chloromethoxyethyl)-trimethylsilane (SEM-Cl) is added and stirring is continued at −20° C. for 5 h. The mixture is then allowed to warm up to room temperature overnight. The reaction is then quenched by addition of 10 ml saturated NH4Cl solution followed by 10 ml water and extracted with 2×40 ml isopropyl acetate. The layers are separated and the organic layer dried over MgSO4, filtered and evaporated. The resulting residue (1.33 g) is purified using column chromatography (dichloromethane:triethylamine=99.5:0.5→dichloromethane:methanol:triethylamine=98.5:1:0.5) to give (S)-5-Biphenyl-4-ylmethyl-1-(2-trimethylsilanylethoxymethyl)pyrrolidin-2-one (1-a, R1=SEM) as a yellow oil. NMR (400 MHz, CDCl3, /ppm): 7.58 (m, 4H); 7.47 (m, 2H); 7.37 (m, 1H); 7.30 (m, 2H); 5.04 (d, J=10.6, 1H); 4.70 (d, J=10.6, 1 H); 4.03 (m, 1H); 3.59 (m, 2H); 3.24 (dd, J=4.2, 13.4, 1H); 2.67 (dd, J=9.1, 13.4, 1H); 2.33 (t, J=8.2, 2 H); 2.10 (m, 1H); 1.81 (m, 1H); 1.00 (m, 2H); 0.06 (s, 9H). MS (ESI, m/e) 382 [M+H]+; 763 [2M+H]+. IR (solution in CH2Cl2, /cm−1): 3057; 2951; 1702; 1487; 1414; 1249; 1073; 859; 836; 759; 697.

Aufarbeitung

  1. stirringstirring
  2. waitis continued at −20° C. for 5 h
  3. temperatureto warm up to room temperature overnight
  4. customThe reaction is then quenched by addition of 10 ml saturated NH4Cl solution
  5. extractionextracted with 2×40 ml isopropyl acetate
  6. customThe layers are separated
  7. dry with materialthe organic layer dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe resulting residue (1.33 g) is purified

Quellen und Nachweise

ORD-Eintrag
ord-43862ceaa19d42db872cd3e887a9a7db
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993785B2

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