Methyl iodide → 3-((S)-(4-chlorophenyl){3-[(1S)-1-(3,5-difluorophenyl)-2-methoxy-2-methylpropyl]azetidin-1-yl}methyl)benzonitrile

HRID 1724225Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1724225
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:17]2[CH2:20][CH:19]([C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=3)[C:22]([OH:25])([CH3:24])[CH3:23])[CH2:18]2)[C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])=[CH:4][CH:3]=1.[CH3:34][Si]([N-][Si](C)(C)C)(C)C.[Na+].IC>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([N:17]2[CH2:20][CH:19]([C@@H:21]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=3)[C:22]([O:25][CH3:34])([CH3:24])[CH3:23])[CH2:18]2)[C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11259875HCID 11259875, Verbindung

Produkt 1

HCID 111675583-((S)-(4-chlorophenyl){3-[(1S)-1-(3,5-difluorophenyl)-2-methoxy-2-methylpropyl]azetidin-1-yl}methyl)benzonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 46.6 mg (0.1 mmole) of 3-((S)-(4-chlorophenyl){3-[(1S)-1-(3,5-difluorophenyl)-2-hydroxy-2-methylpropyl]azetidin-1-yl}methyl)benzonitrile in THF was cooled to −78° C. To this was added 0.3 mL of a 1M solution of NaHMDS in THF. After 10 minutes, 20 uL of iodomethane was added and the solution was allowed to warm to rt. The solution was partitioned between ethyl acetate and water and the organic layer was washed with brine, dried over MgSO4 and concentrated. The residue was filtered through silica gel using 10% ethyl acetate-hexane to afford the title compound; 1H-NMR(CDCl3) δ 1.07 (s, 3H), 1.14 (S, 3H), 2.28 (t, 1H, J=7.5 Hz), 2.74 (d, 1H, J=10.7 Hz), 2.82 (t, 1H, J=7.5 Hz), 3.10-3.16 (m, 2H), 3.19 (s, 1H), 3.62 (m, 1H), 4.29 (s, 1H), 6.67-6.73 (m, 3H), 7.21-7.4 (m, 8H);); Mass Spectrum: m/e=481 (M+1, 35Cl) and 483 (M+1, 37Cl).

Aufarbeitung

  1. customThe solution was partitioned between ethyl acetate and water
  2. washthe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. filtrationThe residue was filtered through silica gel using 10% ethyl acetate-hexane

Quellen und Nachweise

ORD-Eintrag
ord-8acf86325125424583e4ef4e738f21ef
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07485732B2

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