Methyl iodide → HCID 59722686, compound

HRID 1664847Notes

Reaction equation

HRID 1664847 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]2[C:18]([CH:21]([OH:26])[C:22]([F:25])([F:24])[F:23])=[CH:19][N:20]=[C:15]2[C@H:14]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:13][CH2:12]1.I[CH3:36]>O1CCCC1>[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]2[C:18]([CH:21]([O:26][CH3:36])[C:22]([F:24])([F:23])[F:25])=[CH:19][N:20]=[C:15]2[C@H:14]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 59722545HCID 59722545, compound

Product 1

HCID 59722686HCID 59722686, compoundYield 27.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil; 88.3 mg, 2.21 mmol) was added to a solution of tert-butyl (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-ylcarbamate (0.68 g, 1.47 mmol) and iodomethane (92.0 μL, 1.47 mmol) in tetrahydrofuran (20 mL) at 0° C. After 2 h, the mixture was allowed to warm to ambient temperature. After 2 h, additional iodomethane (92.0 μL, 1.47 mmol) and sodium hydride (60% dispersion in mineral oil; 10.0 mg, 0.27 mmol) were added. After 1 h, the reaction was quenched with water and the mixture was extracted with dichloromethane (3×). The organic layer was washed with water, saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→30% ethyl acetate/dichloromethane) gave the title compound (195 mg). MS 476.2 (M+1).

Workup

  1. waitAfter 2 h
  2. waitAfter 1 h
  3. customthe reaction was quenched with water
  4. extractionthe mixture was extracted with dichloromethane (3×)
  5. washThe organic layer was washed with water, saturated brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (100% dichloromethane→30% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-79739154edab4aef96d7d6c4c2aa7eb1
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

Loading…