Methyl iodide → HCID 59722667, compound

HRID 1664839Notes

Reaction equation

HRID 1664839 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]([CH2:21][CH2:22][OH:23])=[CH:19][N:20]=[C:15]2[C@H:14]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:13][CH2:12]1.I[CH3:33]>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]([CH2:21][CH2:22][O:23][CH3:33])=[CH:19][N:20]=[C:15]2[C@H:14]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:30])[CH3:29])[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 59722595HCID 59722595, compound

Product 1

HCID 59722667HCID 59722667, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil; 4.0 mg, 0.112 mmol) was added to a solution of tert-butyl (6S,9R)-6-(2,3-difluorophenyl)-3-(2-hydroxyethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-ylcarbamate (19 mg, 0.047 mmol) and iodomethane (3.0 μL, 0.051 mmol) in tetrahydrofuran (0.5 mL) at 0° C., and the mixture was allowed to warm to ambient temperature. After 18 h, additional sodium hydride (2.0 mg, 0.056 mmol) and iodomethane (3.0 μL, 0.051 mmol) were added. After 1 h, the reaction was quenched with water. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with dichloromethane (2×). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. Purification by silica gel chromatography (100% dichloromethane→94% dichloromethane/methanol) gave the title compound (6 mg). MS 422.1 (M+1).

Workup

  1. waitAfter 1 h
  2. customthe reaction was quenched with water
  3. additionSaturated aqueous sodium bicarbonate was added
  4. extractionthe mixture was extracted with dichloromethane (2×)
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% dichloromethane→94% dichloromethane/methanol)

Sources & evidence

ORD record
ord-ce8e557e113e400fb030a7576c3bfbb7
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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