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

HRID 602718ノート

反応式

HRID 602718 の反応式
[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

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11259875HCID 11259875、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5d29357efe564cf6ac8bf052216cfa95
出典データセット
uspto-grants-2011_03
特許番号
US07906503B2

反応ノート

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