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

HRID 1724225Notes

Reaction equation

HRID 1724225 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-8acf86325125424583e4ef4e738f21ef
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

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